JP2012509338A - Dimeric 1-arylpyrazole derivatives - Google Patents

Abstract

【選択図】なしDimer 1-arylpyrazole compounds of formula (I), (II) or (III), or salts thereof, and use of these compounds against ectoparasites such as insects, arthropods and mites I will provide a.
The obtained compound can be used in animal preparations such as spot-on preparations and pour-on preparations, and can be used for treatment, extermination and prevention of parasitic infections in warm-blooded animals and birds.
[Chemical 1]

[Selection figure] None

Description

This application claims the benefit of priority of US Provisional Patent Application No. 61,116,021, filed on November 19, 2008, the description of which is incorporated herein in its entirety. And
FIELD OF THE INVENTION

(Wherein R ₁ , R _1a , R ₂ , R _2a , R ₃ , R _3a , R ₄ , R _4a , R ₅ , R _5a , R ₁₃ , R _13a , L, Z, Z ₁ and n are (As defined below)
Of dimer 1-arylpyrazole compounds, or salts thereof, and use of these compounds against ectoparasites (including insects and mites).

Animals such as mammals and birds are often susceptible to parasitic infections. These parasites can be ectoparasites such as insects and endoparasites such as filamentous and helminths.
Livestock animals, such as cats and dogs, often infect one or more of the following ectoparasites:
-Fleas (Ctenocephalides felis, Ctenocephalides sp.),
-Ticks (Rhipicephalus sp., Ixodes sp., Dermacentor sp., Amblyomma sp., Etc.),
-Tick (Demodex sp., Sarcoptes sp., Otodectes sp., Etc.),
-Lice (Trichodectes sp., Kheyletiella sp., Linognathus sp., Etc.)
-Flies (Hematobia sp.), Musca sp., Stomoxys sp., Dermatobia sp., Cochliomyia sp.
-Mosquitoes (family Culicidae) etc.
Fleas are particularly problematic because they not only adversely affect the health of animals or humans, but also cause significant mental stress. Further, fleas are also pathogen vectors in animals, such as the dog beetle (Dipylidium caninum), which can infect humans with pathogenic bacteria.

Similarly, ticks are also detrimental to the physical and mental health of animals or humans. However, the most serious problem associated with ticks is that they are vectors of pathogens that cause both human and animal diseases. Major diseases caused by ticks include borreliosis (Lyme disease caused by Borrelia burgdorferi), Babesiosis (or piroplasmosis caused by Babesia sp.) And rickettsiosis (Also known as Rocky Mountain Spotted Fever). Ticks also release toxins that cause inflammation or paralysis in the host. Sometimes these toxins, Ixodes holocyclus in the case of Australian tick bites, are deadly to the host.
Furthermore, ticks and lice are particularly difficult to eradicate because there are very few active substances that act on these parasites and require frequent treatment.
Similarly, livestock are susceptible to parasitic infections. For example, cattle are affected by many parasites. Similarly, arthropod parasites such as fleas, lice, ticks and ticks infect poultry. Parasites commonly found in livestock are of the genus Boophilus, in particular the species of microplus (bovine tick), decoloratus and anulatus. Ticks, such as Boophilus microplus, are particularly difficult to combat because livestock inhabit grass-fed pastures. Other important parasites of cattle and sheep are listed below in order of importance:
(a) Myerses such as Dermatobia hominis (known as Berne in Brazil), Hypoderma, and Cochlyomia hominivorax (Lucaria); Flies that cause sheep miasses, such as the Lucilia cuprina (also known as the Cloverest Strike in Australia, New Zealand and South Africa). These are flies where this larva becomes an animal parasite;
(b) natural flies, adults of which are parasites, e.g. Haematobia irritans (Haematobia irritans);
(c) lice such as Linognathus vituli; and
(d) Mites such as Sarcoptes scabiei and Psoroptes ovis.

The compounds of the present invention include cockroaches, Blatella sp., Moths, Tineola sp., Cutlet worms, Attagenus sp. And Musca domestica. It can also be effective against indoor pests that are not limited to, such as Solenopsis invicta (imported crayfish), termites and the like.
These compounds further include pests that attack stored crops as well as agricultural pests such as aphids (Acyrthiosiphon sp.), Locusts, and cotton weevil, e.g., Triborium sp. It is also useful for immature insects that eat plant tissue.
The above list is not exhaustive and it is well known in the art that other ectoparasites are harmful to animals, humans and crops.
Compounds that exhibit some activity against a wide range of ectoparasites including arthropods and insects are known in the art. One such compound is arylpyrazole, which is, for example, U.S. Pat.Nos. 5,232,940; 5,547,974; 5,608,077; 5,714,191; No. 5,817,688; No. 5,885,607; No. 5,916,618; No. 5,922,885; No. 5,965,491; No. 5,994,386; No. 6,010,710; No. 6,069,157 No. 6,083,519; No. 6,096,329; No. 6,124,339; No. 6,160,002; No. 6,180,798; No. 6,350,771; No. 6,372,774 No. 6,395,906; No. 6,531,501; No. 6,630,499; No. 6,685,954; No. 7,067,548; U.S. Published Application No. 11 / 825,050 All the descriptions in these specifications are included in this specification as a whole. Aryl pyrazoles are also described, for example, in EP 0 234 119, 0 295 117, 0 352 944; 0 780 378; 0 846 686. No. 0 948 485, the description of all of which is included in the present specification.

Aryl pyrazoles are known to have excellent activity against insects such as fleas and ticks. Fipronil is a specific type of 1-N-arylpyrazole that is particularly effective against fleas and ticks and is an active ingredient in Frontline® and Frontline Plus®.
Bis-1-arylpyrazoles containing a disulfide bond in the 4-position of pyrazole are used as intermediates in the synthesis to monomer 1-arylpyrazoles in EP 0 295 117. The derivatives themselves are not disclosed therein as insecticides. Bis-N-phenylpyrazozole derivatives linked by the 5-position of pyrazole are described in US Application Publication No. 11 / 615,668.
However, ectoparasite eradication agents may not only differ in their efficacy against specific parasites, but may also vary in manufacturing costs. Furthermore, the results of ectoparasite eradication agents may not always be satisfactory because the parasites are resistant to therapeutic agents, as in the case of carbamates, organophosphorus compounds, pyrethroids, for example. is there. As resistance issues arise, modern insecticide studies must also take into account the spectrum of action, side effect profiles for animal hosts, and dosing convenience.

Accordingly, there remains a need in the art for new antiparasitic compositions that act more effectively and rapidly to treat and protect animals, such as mammals, fish, and birds, from a wide range of parasites. . There is a need in the art for antiparasitic formulations that are easy to use for any type of livestock, regardless of size or type of hair, and that do not require administration throughout the body of a mammal, fish or bird. Furthermore, the formulation must be effective for a long time, thereby reducing the number of applications.
All references cited or indicated in this specification ("references cited in this specification"), and all references cited or indicated in the references cited in this specification. Is expressly included herein, together with manufacturer's instructions, descriptions, product specifications, and product sheets for the products listed herein or in the literature contained herein. Can be used to implement
Citation or identification of documents in this application is not an admission that such documents are available as prior art to the present invention.

The present invention is for the treatment or prevention of parasites of animals (both wild animals and livestock), for example, livestock animals such as cats, dogs, horses, chickens, sheep, goats, pigs, turkeys, cows and companion animals. It is an object of the present invention to provide and provide novel compounds, compositions and uses thereof aimed at removing parasites normally encountered by such animals from these hosts .
The present invention also provides effective and sustained control of ectoparasites such as fleas, ticks, ticks, mosquitoes, flies and lice. The present invention is also effective against endoparasites, tapeworms, nematodes, such as filamentous worms, and roundworms of the digestive tract of animals and humans.
The 1-arylpyrazole compounds of the present invention, alone or in combination, provide protection against ectoparasites that can include efficacy rate, sustained efficacy (e.g., at least 1 month), high efficacy, and high selectivity. Can do.
One aspect of the present invention is to provide (1) a dimeric 1-arylpyrazole compound of formula (I); or (2) a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n - and -S ( O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.
A second aspect of the present invention is to provide (1) a dimeric 1-arylpyrazole compound of formula (II); or (2) a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.
A third aspect of the present invention is to provide (1) a dimeric 1-arylpyrazole compound of formula (II); or (2) a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R _{7, -C (= NR 7)} R 8, -C (= NR7) NR 11 R 12, -S (O) nR 11, and selected from the group consisting of SF _5;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 SO} 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) - , -C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - C (= NR 7) NR 11, -S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

A fourth aspect of the invention is to provide a composition for the treatment of animals against ectoparasites comprising the compound of the invention and an acceptable carrier.
A fifth aspect of the present invention provides a 1-arylpyrazole compound / composition of the present invention against ectoparasites (eg, arthropods) in veterinary medicine or livestock breeding, public health, or agricultural or horticultural crops. It is to provide an insecticidal method using.
The fifth aspect of the present invention is a high activity and improvement obtained by optimizing chemical properties, physical properties and biological properties such as solubility, melting point, stability, electronic parameters, steric parameters. It is to give the user and the environment a compound with high safety.
A seventh aspect of the present invention provides a composition comprising a dimeric 1-arylpyrazole compound of the present invention, using an actual or putative growth phase host or early host, such as an animal, bird (wild or domestic). Or a method to prevent or block infection of a parasite-derived disease from a human to a second actual or putative proliferative or early host such as an animal, bird or human.
USPTO (35 USC 112, No. 1), where the present invention discloses the disclaimer of the product, the method of manufacturing the product or the method of using the product, to which the applicant is entitled and thereby described. ) Or EPO (EPC Clause 83) specification and enablement requirements, compounds, products, methods of producing products or methods of using products already disclosed within the scope of the present invention. It is noted that it is not intended to be included. Therefore, the intent of the present invention is as follows: U.S. Pat.Nos. 5,122,530; 5,885,607; 6,010,710; 6,083,519; 6,096,329; 6,685,954 European Patent No. 0 234 119, European Patent No. 0 295 117 (U.S. Pat.No. 5,232,940; No. 5,547,974; No. 5,608,077; No. 5,714,191) No. 5,916,618, No. 6,372,774); European Patent No. 0 352 944 (U.S. Pat.No. 4,963,575); European Patent No. 0 780 378 (U.S. Pat.No. 5,817,688) No. 5,922,885; No. 5,994,386; No. 6,124,339; No. 6,180,798; No. 6,395,906); EP 0 846 686 (U.S. Pat.No. 6,069,157) The prior art, including but not limited to the prior art cited herein, is clearly disclosed in the prior art? Does not specifically include compounds, products, products or methods of making compounds, or methods of using products or compounds, where novelty is revoked by prior art, Incorporation of a waiver into the claims regarding the compounds, products, methods of producing the products or methods of using the products already disclosed. Specifically, the compounds of the present invention are not intended to encompass fipronil or fipronil derivatives already disclosed.
These and other embodiments are disclosed or become obvious and encompassed by the following detailed description.

The following terms used in this specification have meanings based on these unless otherwise specified. In this disclosure and in the claims, terms such as “comprising”, “including”, “including”, and “having” have the meanings based on these in US Patent Law, and “include”, “include” As well as "being essentially" or "being essentially" has the meaning under U.S. Patent Law, and the term is not limited and is listed More than the listed ones are allowed, but exclude prior art embodiments, unless the basic or novel features are changed by more than the ones listed.
Unless indicated in detail or otherwise apparent by context, “active agent” or “active ingredient” or “therapeutic agent” as used herein refers to a dimeric 1-arylpyrazole compound of the invention.
In this disclosure and the appended claims and / or claims, the term “dimeric 1-arylpyrazole” or “dimeric arylpyrazole” as used to describe the invention is intended to mean all stereoisomers thereof. It is also noted that it is intended to include body and crystalline forms (including hydrated, polymorphic and amorphous forms having a crystal structure of up to 15% by weight).
The term “animal” as used herein includes all mammals, birds and fish, and also includes all vertebrates including humans. It also includes individual animals that can be placed in all developmental stages including embryonic and fetal stages.

For the purposes of this application, the following terms have the following definitions unless otherwise indicated in the specification:
(1) Alkyl means both straight and branched carbon chains. An individual alkyl group means a straight chain (eg, butyl = n-butyl). In one embodiment of alkyl, the number of carbon atoms is 1-20, in other embodiments of alkyl, the number of carbon atoms is 1-8, and in still other embodiments of alkyl, carbon atoms The number of is 1-4. Other ranges of carbon numbers are contemplated depending on the position of the alkyl moiety on the molecule.
(2) Alkenyl refers to both straight and branched carbon chains having at least one carbon-carbon double bond. In one embodiment of alkenyl, the number of double bonds is 1-3, and in another embodiment of alkenyl, the number of double bonds is one. In one embodiment of alkenyl, the number of carbon atoms is 2-20, in other embodiments of alkenyl, the number of carbon atoms is 2-8, and in yet another embodiment of alkenyl, The number of is 2-4. Other ranges of carbon-carbon double bonds and carbon numbers are possible depending on the position of the alkenyl moiety on the molecule.
(3) Alkynyl means both straight and branched carbon chains having at least one carbon-carbon triple bond. In one embodiment of alkynyl, the number of triple bonds is 1-3, and in another embodiment of alkynyl, the number of triple bonds is 1. In one embodiment of alkynyl, the number of carbon atoms is 2-20, in other embodiments of alkynyl, the number of carbon atoms is 2-8, and in still other embodiments of alkynyl, The number is 2-4. Other ranges of carbon-carbon triple bonds and carbon numbers are contemplated depending on the position of the alkenyl moiety in the molecule.
(4) Aryl means a C ₆ -C ₁₀ aromatic ring structure. In one embodiment of aryl, the moiety is phenyl, naphthyl, tetrahydronaphthyl, phenylcyclopropyl, and indanyl; in another embodiment of aryl, the moiety is phenyl.
(5) Alkoxy means —O-alkyl, where alkyl is as defined in (1).
(6) Thioalkyl means —S-alkyl, wherein alkyl is as defined in (1).

(7) Oxo means C═O.
(8) Oximino means C═N—OH.
(9) Alkoxyimino means C = NO-alkyl, where alkyl is as defined in (1).
(10) Cyclo as a prefix (e.g., cycloalkyl, cycloalkenyl, cycloalkynyl) means a saturated or unsaturated ring structure having 3-8 carbon atoms in the ring, the scope of which is defined above for aryl Is distinct and different. In one embodiment of cyclo, the ring size range is 4-7 carbon atoms, and in another embodiment of cyclo, the ring size range is 3-4. Other ranges of carbon numbers are contemplated depending on the position of the cyclo moiety in the molecule.
(11) Halogen means the atoms fluorine, chlorine, bromine and iodine. The designation of “halo” (eg, indicated by the term haloalkyl) ranges from a single substitution to a perhalo substitution (eg, methyl and chloromethyl (—CH ₂ Cl), dichloromethyl (—CHCl ₂ ), or trichloromethyl (— Means all degrees of substitution up to (shown as CCl ₃ ). The designation “halo” (eg, indicated by the term haloalkyl) also means substitution with one or more independently selected halogen atoms (eg, methyl and dichloromethyl (—CHCl ₂ ), chlorofluoromethyl) (-CHClF), or indicated as dichlorofluoromethyl (-CFCl _2)).
(12) Heterocycle, heterocyclic or heterocyclo is fully saturated, including aromatic (ie, “heteroaryl”) having at least one heteroatom in a ring containing at least one carbon atom, or By unsaturated cyclic group is meant, for example, a 4-7 membered monocyclic system, a 7-11 membered bicyclic system, or a 10-15 membered tricyclic system. Each ring of the heterocyclic group containing a heteroatom may have 1, 2, 3 or 4 heteroatoms selected from a nitrogen atom, an oxygen atom and / or a sulfur atom. The atom may be oxidized if necessary, and the nitrogen heteroatom may be quaternized if necessary. The heterocyclic group may be attached to any heteroatom or carbon atom of the ring or ring system.

Examples of monocyclic heterocyclic groups include pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, imidazolidinyl, oxazolyl, oxazolidinyl, isoxalinyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, isothiazolyl, isothiazolyl, Tetrahydrofuryl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, azepinyl, 4-piperidonyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, Tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinyl sulfone, 1,3-dioxolane and te Rahidoro 1,1-dioxothienyl, triazolyl, triazinyl, and the like.
Exemplary bicyclic heterocyclic groups include indolyl, benzothiazolyl, benzoxazole, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzofuryl, chromonyl, coumarinyl Benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridinyl (eg furo [2,3-c] pyridinyl, furo [3,2-b] pyridinyl, or furo [2,3-b] pyridinyl), dihydroisoin A drill, dihydroquinazolinyl (for example, 3,4-dihydro-4-oxoquinazolinyl), tetrahydroquinolinyl and the like.
Exemplary tricyclic heterocyclic groups include carbazolyl, benzindolyl, phenanthrolinyl, acridinyl, phenanthridinyl, xanthenyl and the like.
The first object of the present invention is to provide a compound of formula (I); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
The linker is optionally independently one or more groups selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. May be substituted;
n is independently 0, 1 or 2.

Another embodiment of the first object of the present invention provides a compound of formula (I); or a salt thereof, wherein
R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy and haloalkoxy;
R ₄ and R _4a are independently selected from the group consisting of halogen, R ₇ , R ₈ , —S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( _{= NR 7) NR 11 R 12} , -C (= S) NR 11 R 12, selected from the group consisting of -NR ₁₁ R ₁₂ and _{-N = C (R 11) NR} 6,;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
The aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a are _{independently, -C (= NR 7) -} , - C (= NR 8) -, - C (= O) -, - C (= O) NR 11 -, - C ( _{= S) NR 11 -, -} S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, May contain S, P or Si atoms;
The linker is optionally independently one or more groups selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. May be substituted;
n is independently 0, 1 or 2.

Another embodiment of the first object of the present invention provides a compound of formula (I); or a salt thereof, wherein
R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are independently selected from the group consisting of halogen, haloalkyl, —S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently selected from the group consisting of alkyl, haloalkyl, —NR ₁₁ R ₁₂ , and —N═C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and alkyl;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl and heteroaryl groups may be optionally substituted with one or more groups independently selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R11, -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Is;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are _{independently, -C (= NR 7) -} , - C (= NR 8) -, - C (= O) -, - C (= O) NR 11 -, - C ( _{= S) NR 11 -, -} S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof;
These may optionally contain one or more N, O, S, P, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted with;
n is independently 0, 1 or 2.

Another embodiment of the first object of the present invention provides a compound of formula (I); or a salt thereof, wherein
R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are hydrogen;
R ₁₃ and R _13a are -S (O) _n- ;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, and optionally one or more N atoms, O atoms, S atoms , May contain P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.
Another embodiment of the first object of the present invention provides a compound of formula (I); or a salt thereof, wherein
R ₁ and R _1a are cyano;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are hydrogen;
R ₁₃ and R _13a are -S (O) _n- ;
L is alkyl or haloalkyl;
n is 2.
A second object of the present invention is to provide a compound of formula (II); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl and heteroaryl groups may optionally be independently substituted with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) nR ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C ( = O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Is;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, May contain S, P or Si atoms;
The linker is optionally independently one or more groups selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. May be substituted;
n is independently 0, 1 or 2.

Another embodiment of the second object of the present invention provides a compound of formula (II); or a salt thereof, wherein:
R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( _{= NR 7) NR 11 R 12} , -C (= S) NR 11 R 12, selected from the group consisting of -NR ₁₁ R ₁₂ and _{-N = C (R 11) NR} 6,;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Is replaced by one or more groups selected from the group consisting of:
R is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group are independently substituted with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ as necessary;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a bond, -O -, - S (O ) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

Another embodiment of the second object of the present invention provides a compound of formula (II), wherein:
R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, haloalkyl, —NR ₁₁ R ₁₂ , and —N═C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and alkyl;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl and heteroaryl groups may be optionally substituted independently with one or more groups selected from R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a is independently a bond, -O -, - S (O ) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

Another embodiment of the second object of the present invention provides a compound of formula (II); or a salt thereof, wherein:
R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R11, and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are independently selected from the group consisting of a bond and -S (O) _n- ;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted with;
n is independently 0, 1 or 2.

Another embodiment of the second object of the present invention provides a compound of formula (II); or a salt thereof, wherein:
R ₁ and R _1a are cyano;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are a bond;
L is alkyl or haloalkyl;
n is 2.
A third object of the present invention is to provide a compound of formula (III); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 SO} 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) - , -C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - C (= NR 7) NR 11, -S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

Another embodiment of the third object of the present invention provides a compound of formula (III); or a salt thereof, wherein:
R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ and -C (S) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently selected from the group consisting of halogen, R ₇ , R ₈ , —S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl and heteroaryl groups may optionally be independently substituted with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 SO} 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) - , -C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - C (= NR 7) NR 11, -S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, May contain S, P or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

Another embodiment of the third object of the present invention provides a compound of formula (III); or a salt thereof, wherein:
R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-diacyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are independently selected from the group consisting of halogen, haloalkyl, —S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and alkyl;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a is independently a _{bond, -NR 11 SO 2 NR 11 -} , - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) -, - C ( _{= O) NR 11 -, -} C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

Another embodiment of the third object of the present invention provides a compound of formula (III); or a salt thereof, wherein:
R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R ₁₃ are a bond;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

Another embodiment of the third object of the present invention provides a compound of formula (III); or a salt thereof, wherein:
R ₁ and R _1a are cyano;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
Z and Z ₁ are CR ₃ ;
R ₁₁ is haloalkyl;
R ₁₃ and R _13a are a bond;
L is alkyl or haloalkyl;
n is 2.
The object of the present invention is further to a composition for treating animals against ectoparasites and / or endoparasites comprising any one compound of formulas (I)-(III) and an acceptable carrier. Is to provide.
The object of the present invention is still further any of the formulas (I)-(III) in the manufacture of a medicament for the therapeutic and / or prophylactic treatment of animals against ectoparasites and / or endoparasites. It is to provide the use of a composition comprising one compound.
It is still a further object of the present invention to provide an insecticide composition comprising any one compound of formula (I)-(III) and an acceptable carrier.

The object of the present invention still further provides the use of any one compound of formula (I)-(III) in the manufacture of a composition for combating pests.
The object of the invention is still further a process for the preparation of an insecticide composition, characterized in that any one compound of the formulas (I)-(III) is mixed with an extender and / or a surfactant. And providing the method.
The object of the present invention is still further a method for controlling pests, comprising any one compound of formula (I)-(III) or any one compound of formula (I)-(III) It is to provide said method wherein the composition is allowed to act on pests and / or their environment or on plants, plant parts, seeds, soils, areas, materials or spaces to keep them free of pests.
The object of the present invention is still further the use of any one compound of formula (I)-(III) or a composition comprising any one compound of formula (I)-(III) for combating pests Is to provide.
The object of the invention still further comprises a composition comprising any one compound of formula (I)-(III) or any one compound of formula (I)-(III) for treating a genetically modified plant Is to provide the use of things.
Where applicable, acid or base salts of the dimeric arylpyrazoles provided herein are also contemplated within the scope of the present invention.
The term “acid” contemplates all pharmaceutically acceptable inorganic or organic acids. Examples of the inorganic acid include hydrobromic acid such as hydrobromic acid and hydrochloric acid, sulfuric acid, phosphoric acid and nitric acid. Organic acids include all pharmaceutically acceptable aliphatic carboxylic acids, alicyclic carboxylic acids, aromatic carboxylic acids, dicarboxylic acids, tricarboxylic acids and fatty acids. In one embodiment of the acid, the acid is a straight chain or branched chain saturated or unsaturated C ₁ -C ₂₀ aliphatic carboxylic acid (which is optionally substituted with a halogen group, a hydroxyl group). ), Or a C ₆ -C ₁₂ aromatic carboxylic acid. Examples of such acids are carbonic acid, formic acid, fumaric acid, acetic acid, propionic acid, isopropionic acid, valeric acid, α-hydroxy acids such as glycolic acid and lactic acid, chloroacetic acid, benzoic acid, methanesulfonic acid, salicylic acid It is. Examples of dicarboxylic acids include oxalic acid, malic acid, succinic acid, tartaric acid and maleic acid. An example of a tricarboxylic acid is citric acid. Fatty acids include all pharmaceutically or veterinary acceptable saturated or unsaturated aliphatic or aromatic carboxylic acids having 4 to 24 carbon atoms. Examples include butyric acid, isobutyric acid, sec-butyric acid, lauric acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and phenyl stearic acid. Other acids include gluconic acid, glucoheptonic acid and lactobionic acid.

The term “base” contemplates all pharmaceutically or veterinary acceptable inorganic or organic bases. Examples of such a base include alkali metal salts and alkaline earth metal salts such as lithium, sodium, potassium, magnesium or calcium salts. Examples of the organic base include general hydrocarbylamine salts and heterocyclic amine salts, and examples thereof include morpholine salts and piperidine salts.
The ectoparasite eradication compositions of the present invention comprise a dimeric arylpyrazole and an acceptable carrier, such as an animal acceptable carrier or an ectoparasite eradicable carrier. In one embodiment of the invention, the ectoparasite-acceptable carrier is an organic solvent commonly used in pharmaceutical technology. These organic solvents are, for example, can be found in ^{Remington Pharmaceutical Science, 16 th Edition (} 1986). Examples of these solvents include acetone, ethyl acetate, methanol, ethanol, isopropanol, dimethylformamide, dichloromethane, or diethylene glycol monoethyl ether (Transcutol). These solvents can be added with various excipients, such as C ₈ -C ₁₀ caprylic / capric triglycerides (Estasan or Miglyol 812), oleic acid or propylene glycol depending on the type of phase desired.
The compositions of the present invention can be in various forms including but not limited to oral formulations, injectable formulations, topical formulations, transdermal formulations, or subcutaneous formulations.

The composition of the present invention is in a form suitable for oral use, e.g., bait (see, e.g., U.S. Pat. Capsules, soft capsules, emulsions, aqueous suspensions, oily suspensions, aqueous solutions, oily solutions, oral drench preparations, dispersible powders, granules, syrups or elixirs, enteric preparations, pastes obtain. Compositions intended for oral use can be prepared according to methods known in the art for the manufacture of pharmaceutical compositions, and such compositions can be formulated with sweeteners to provide pharmaceutically elegant and delicious formulations. One or more substances selected from the group consisting of a bitter agent, a flavoring agent, a coloring agent, and a preservative can be contained.
Tablets may contain the active ingredient in admixture with non-toxic pharmaceutically acceptable excipients that are suitable for the manufacture of tablets. These excipients include, for example, inert diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents such as corn starch, or alginic acid; binders such as starch , Gelatin or acacia, and lubricants such as magnesium stearate, stearic acid or talc, tablets may be uncoated or coated with known techniques to disintegrate or absorb in the gastrointestinal tract Can be delayed, thereby providing a long-lasting effect. For example, a time delay material such as glyceryl monostearate or glyceryl distearate may be employed. These can also be coated with the techniques described in US Pat. Nos. 4,256,108, 4,166,452, and 4,265,874 to form osmotic therapeutic tablets for controlled release.

Formulations for oral use may be hard gelatin capsules in which the active ingredient is mixed with an inert solid diluent such as calcium carbonate, calcium phosphate or kaolin. Capsules may be soft gelatin capsules in which the active ingredient is mixed with water or a miscible solvent such as propylene glycol, ethanol, or an oil medium such as peanut oil, liquid paraffin, or olive oil.
The composition of the present invention may be in the form of an oil-in-water or water-in-oil emulsion. The oily phase may be a vegetable oil, for example olive oil or arachis oil, or a mineral oil, for example liquid paraffin or mixtures of these. Suitable emulsifiers include naturally occurring phosphatides such as soy, lecithin, esters or partial esters derived from fatty acids and hexitol anhydrides, such as sorbitan monooleate, condensation products of said partial esters and ethylene oxide, such as It can be polyoxyethylene sorbitan monooleate. The emulsion may contain sweetening, bittering, flavoring, and / or preservatives.
In one embodiment of the formulation, the composition of the present invention is in the form of a microemulsion. Microemulsions are well suited as liquid carrier excipients. Microemulsions are quaternary systems comprising an aqueous phase, an oil phase, a surfactant and a cosurfactant. These are translucent and isotropic liquids.
A microemulsion is composed of a stable dispersion of fine droplets of an aqueous phase in an oil phase, or conversely, fine droplets of an oil phase in an aqueous phase. The size of these droplets is less than 200 nm (1000-100,000 nm for emulsions). The interfacial thin film is composed of alternating surface-active (SA) molecules and co-surface-active (Co-SA) molecules that can spontaneously form microemulsions by reducing interfacial tension.

In one embodiment of the oil phase, the oil phase may be formed from mineral or vegetable oils, from unsaturated polyglycosylated glycerides or triglycerides, or from mixtures of such compounds. In one embodiment of the oil phase, the oil phase is composed of triglycerides. In another embodiment of the oil phase, the triglyceride is a medium chain triglyceride, such as C ₈ -C ₁₀ caprylic / capric triglyceride. Other embodiments of the oil phase represent a% v / v range selected from the group consisting of about 2 to about 15% of the microemulsion; about 7 to about 10%; about 8 to about 9% v / v. Become.
Examples of the aqueous phase include water or glycol derivatives such as propylene glycol, glycol ether, polyethylene glycol or glycerol. In one embodiment of the glycol derivative, the glycol is selected from the group consisting of propylene glycol, diethylene glycol monoethyl ether, dipropylene glycol monoethyl ether, and mixtures thereof. In general, the aqueous phase will represent a proportion of about 1 to about 4% v / v of the microemulsion.
Surfactants for microemulsions include diethylene glycol monoethyl ether, dipropylene glycol monomethyl ether, polyglycolized C ₈ -C ₁₀ glycerides or polyglyceryl-6 dioleate. In addition to these surfactants, co-surfactants include short chain alcohols such as ethanol and propanol.
Some compounds are common to the above three components: the aqueous phase, the surfactant and the cosurfactant. However, the use of different components for each component of the same formulation is well within the level of ordinary skill in the art. In one embodiment for the amount of surfactant / co-surfactant, the ratio of co-surfactant to surfactant will be from about 1/7 to about 1/2. In other embodiments for the amount of co-surfactant, the ratio will be from about 25 to about 75% v / v surfactant and from about 10 to about 55% v / v co-surfactant in the microemulsion.

Oily suspensions may be formulated by suspending the active ingredient in a vegetable oil, for example arachis oil, olive oil, sesame oil or coconut oil, or in a mineral oil such as liquid paraffin. Oily suspensions may contain a thickening agent, for example beeswax, hard paraffin or cetyl alcohol. Sweetening agents such as sucrose, saccharin or aspartame, bittering agents, and flavoring agents can be added to provide a palatable oral preparation. These compositions can be preserved by the addition of an anti-oxidant such as ascorbic acid, or other known preservatives.
Aqueous suspensions can contain the active materials in admixture with excipients suitable for the manufacture of aqueous suspensions. Such excipients are suspending agents such as sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethylcellulose, sodium alginate, polyvinylpyrrolidone, gum tragacanth, acacia gum; dispersants or wetting agents are naturally occurring phosphatides For example, lecithin, or a condensation product of an alkylene oxide and a fatty acid, such as polyoxyethylene stearate, or a condensation product of an ethylene oxide and a long chain aliphatic alcohol, such as heptadecaethyleneoxycetanol or ethylene oxide, and a fatty acid. Condensation products with partial esters derived from hexitol, for example derived from polyoxyethylene sorbitol monooleate or ethylene oxide, fatty acids and hexitol anhydrides Condensation products of ethylene oxide with partial esters, for example polyethylene sorbitan monooleate. Aqueous suspensions contain one or more preservatives, such as ethyl or n-propyl, p-hydroxybenzoic acid, one or more colorants, one or more flavoring agents, and one or more sweetening agents and / Or bittering agents such as those indicated above may be included.

Dispersible powders and granules suitable for preparation of an aqueous suspension by the addition of water provide the active ingredient in admixture with a dispersing or wetting agent, suspending agent and one or more preservatives. Suitable dispersing or wetting agents and suspending agents are exemplified above. Other excipients may be present, for example sweetening, bittering, flavoring and coloring agents.
Syrups and elixirs may be formulated with sweetening agents, for example glycerol, propylene glycol, sorbitol or sucrose. Such formulations may also contain a demulcent, a preservative, flavoring and / or coloring agent.
In other embodiments of the invention, the composition may be in a paste dosage form. Examples of embodiments in paste dosage form include, but are not limited to, those described in US Pat. Nos. 6,787,342 and 7,001,889. In addition to the active agent of the present invention, the paste may also contain fumed silica; a viscosity modifier; a carrier; optionally an absorbent; and optionally a colorant, stabilizer, surfactant, or preservative.
The method of preparing the paste formulation is:
(a) dissolving or dispersing the active agent in the carrier by mixing;
(b) adding fumed silica to a carrier containing dissolved activator compound and mixing until silica is dispersed in the carrier;
(c) allowing the intermediate formed in b) to settle for a time sufficient to cause the air that has entered during step (b) to flow out;
(d) including a step of adding a viscosity modifier to the intermediate while mixing to obtain a uniform paste.

The above steps are illustrative and are not limited to these. For example, step (a) can be the last step.
In one embodiment of the formulation, the formulation is a paste comprising an active compound, fumed silica, a viscosity modifier, an absorbent, a colorant; and a hydrophilic carrier that is triacetin, monoglyceride, diglyceride, or triglyceride.
Pastes include PEG 200, PEG 300, PEG 400, PEG 600, monoethanolamine, triethanolamine, glycerol, propylene glycol, polyoxyethylene (20) sorbitan monooleate (polysorbate 80 or Tween 80), and polyoxamers (e.g. , Pluronic L 81), a viscosity modifier selected from the group consisting of; magnesium carbonate, calcium carbonate, starch, and an absorbent selected from the group consisting of cellulose and derivatives thereof; and titanium dioxide, iron oxide, and FD & C Blue # 1 aluminum A colorant selected from the group consisting of lakes may be included, but is not limited thereto.
The composition can be a sterile injectable aqueous or oleaginous suspension. This suspension may be formulated according to the known art using those suitable dispersing or wetting agents and suspending agents which have been mentioned above. The sterile injectable preparation may be a sterile injectable solution or suspension in a nontoxic parenterally acceptable diluent or solvent, for example as a solution in 1,3-butanediol. Among the acceptable excipients and solvents, water, Ringer's solution and physiological saline can be used. Cosolvents such as ethanol, propylene glycol or polyethylene glycol may be used. Preservatives such as phenol or benzyl alcohol may be used.

In addition, sterile fixed oils are commonly employed as a solvent or suspending medium. For this purpose, non-irritating fixed oils comprising synthetic monoglycerides or diglycerides may be used. In addition, fatty acids such as oleic acid are used in the preparation of injectables.
Topical, transdermal and subcutaneous formulations include emulsions, creams, ointments, gels, pastes, powders, shampoos, pour-on formulations, ready-to-use formulations, spot-on solutions, and suspensions. Can be. Dispersing a compound of the present invention through an animal gland (e.g., sebaceous gland) by topical application of a compound of the present invention, or a composition comprising at least one compound of the present invention in an active agent therein, a spot-on composition, and The active agent can be achieved systemically (plasma concentration) or throughout the hair. If the compound is dispersed throughout the gland, the gland can act as a reservoir and thereby be long-lasting, eg, effective for 1-2 months. Spot-on formulations are typically applied to local areas, meaning areas other than the entire animal. In one embodiment of the local region, the position is between both shoulders. In other embodiments, the local region is a stripe, such as a stripe from the head to the tail of an animal.
Pour-on formulations are described, for example, in US Pat. No. 6,010,710. Pour-on formulations are advantageously oily and generally contain a diluent or excipient, and also a solvent for the active ingredient (e.g. an organic solvent) if the active ingredient is not soluble in the diluent. Including.
Examples of organic solvents that can be used in the present invention include acetyl tributyl citrate, fatty acid esters such as dimethyl ester, diisobutyl adipate, acetone, acetonitrile, benzyl alcohol, butyl diglycol, dimethylacetamide, dimethylformamide, and dipropylene glycol n-butyl ether. , Ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol monomethyl ether, liquid polyoxyethylene glycol, propylene glycol, 2-pyrrolidone (for example, N-methylpyrrolidone), diethylene glycol mono Ethyl ether, ethylene glycol and diethyl phthalate, or a small amount of these solvents Both including but two mixtures are not limited to.

Vegetable oils such as soybean oil, peanut oil, castor oil, corn oil, cottonseed oil, olive oil, grape seed oil, sunflower oil, etc. as excipients or diluents; mineral oils such as, but not limited to, petrolatum, paraffin, silicone, etc. Mention may be made of aliphatic or cyclic hydrocarbons, or medium-chain (eg C8-C12) triglycerides.
In other embodiments of the present invention, emollients and / or diffusing agents and / or film forming agents will be added. One embodiment of the emollient and / or diffusing agent and / or film-forming agent is a substance selected from the group consisting of:
(a) polyvinyl pyrrolidone, polyvinyl alcohol, copolymer of vinyl acetate and vinyl pyrrolidone, polyethylene glycol, benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylenated sorbitan ester; lecithin, sodium carboxymethylcellulose, silicone oil, polydiorganosiloxane oil ( For example, polydimethylsiloxane (PDMS) oil), such as those containing silanol functional groups, or 45V2 oil,
(b) Alkaline stearate, sodium stearate, potassium stearate or ammonium stearate; calcium stearate, triethanolamine stearate; sodium abietic acid; alkyl sulfates (for example, sodium lauryl sulfate, sodium cetyl sulfate); dodecylbenzenesulfone Sodium carbonate, sodium dioctyl sulfosuccinate; anionic surfactants such as fatty acids (eg, those derived from coconut oil),
(c) formula ^{N + R'R "R"'R}"" Y - ( wherein, R groups, if necessary, may be a hydroxylated hydrocarbon radical, Y ^- is a halogen anion, a sulfate anion, A cationic surfactant such as a water-soluble quaternary ammonium salt of a strong acid anion such as a sulfonate anion; among the cationic surfactants, cetyltrimethylammonium bromide may be used,
(d) an amine salt of the formula N ⁺ R'R "R '" (wherein the R group may optionally be a hydroxylated hydrocarbon group); among cationic surfactants octadecyl Amine hydrochloride can be used,
(e) an optionally polyoxyethylenated sorbitan ester (for example, polysorbate 80), polyoxyethylenated alkyl ether; polyoxypropylated fatty alcohols such as polyoxypropylene-styrene ether; polyethylene glycol stearate Nonionic surfactants, such as polyoxyethylenated derivatives of castor oil, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids, copolymers of ethylene oxide and propylene oxide,
(f) an amphoteric surfactant such as a substituted lauryl compound of betaine, and
(g) A mixture of at least two of these substances.

The solvent will be used depending on the concentration of the activator compound and the solubility in this solvent. It is required that the volume can be minimized. 100% with excipients.
In one embodiment of the amount of emollient, the emollient is used in a proportion selected from the group consisting of about 0.1 to about 10% by volume and about 0.25 to 5% by volume.
In other embodiments of the invention, the composition may be in the form of a ready-to-use solution as described in US Pat. No. 6,395,765. In addition to the activator compound, the ready-to-use solution may contain a crystallization inhibitor, an organic solvent and an organic co-solvent.
The crystallization inhibitor may be present in a proportion selected from the group consisting of about 1 to about 20% (w / v) and about 5 to about 15% (w / v). Acceptable inhibitors are those that produce little or no crystals upon addition (less than 10 crystals).
The organic solvent has a dielectric constant in the range selected from the group consisting of about 10 to about 35 and about 20 to about 30, and the content of the organic solvent in the entire composition supplements the composition to 100% composition. It represents the amount to make. The organic co-solvent has a boiling point selected from the range consisting of less than 100 ° C and less than 80 ° C, and has a dielectric constant in the range selected from the group consisting of about 10 to about 40, and about 20-30. The co-solvent may be present in the composition at an organic co-solvent / organic solvent mass / mass (W / W) ratio of about 1/15 to about 1/2. Co-solvents are volatile to act as drying accelerators and are miscible with water and / or organic solvents.

Crystallization inhibitors useful in the present invention include but are not limited to the following substances:
(a) Polyvinylpyrrolidone, polyvinyl alcohol, copolymers of vinyl acetate and vinyl pyrrolidone, polyethylene glycol, benzyl alcohol, mannitol, glycerol, sorbitol or sorbitan polyoxyethylenated esters; lecithin or sodium carboxymethylcellulose; or acrylic acid derivatives such as , Methacrylate etc .;
(b) anionic surfactants such as alkaline stearates (eg sodium stearate, potassium stearate or ammonium stearate); calcium stearate or triethanolamine stearate; sodium abietic acid; alkyl sulfates, sodium lauryl sulfate And sodium cetyl sulfate; but not limited to; sodium dodecylbenzenesulfonate or sodium dioctylsulfosuccinate; or fatty acids (eg, coconut oil);
(c) Formula N ⁺ R'R''R '"R""Y ⁻ (wherein the R groups are the same or different and optionally a hydroxylated hydrocarbon group, Y ⁻ is an anion of a strong acid) Water-soluble quaternary ammonium salts of, for example, halogen anions, sulfate anions, sulfonate anions; cetyltrimethylammonium bromide is one of the cationic surfactants that can be used;
(d) an amine salt of the formula N ⁺ R′R ″ R ′ ”(wherein R may be the same or different and may optionally be a hydroxylated hydrocarbon radical); octadecylamine hydrochloride is used One of the possible cationic surfactants;
(e) Nonionic surfactants, such as esters which may be optionally polyoxyethylenated, such as sorbitan, such as polysorbate 80, or polyoxyethylenated alkyl ethers; polyethylene glycol stearate, polyoxyethylene in castor oil Derivatives, polyglycerol esters, polyoxyethylenated fatty alcohols, polyoxyethylenated fatty acids or copolymers of ethylene oxide and propylene oxide;
(f) an amphoteric surfactant, such as a substituted lauryl compound of betaine; or
(g) A mixture of at least two compounds listed in the above (a)-(f).

In one embodiment of a crystallization inhibitor, a crystallization inhibitor pair will be used. Such pairs include, for example, a combination of a polymer type film former and a surface active agent. These agents can be selected from the above compounds as crystallization inhibitors.
In one embodiment of the film forming agent, the material has a polymeric form and includes, but is not limited to, various grades of polyvinyl pyrrolidone, polyvinyl alcohol, and copolymers of vinyl acetate and vinyl pyrrolidone.
In one embodiment of the surfactant, the material includes, but is not limited to, one made of a nonionic surfactant. In another embodiment of the surfactant, the material is a polyoxyethylenated ester of sorbitan. In yet another embodiment of the surfactant, the material includes various grades of polysorbate, such as polysorbate 80.
In other embodiments of the present invention, the film former and surfactant may be combined in similar or identical amounts within the limits of the total amount of crystallization inhibitors described above.
Pairs constructed in this way are notable to adhere to the goal of not crystallizing on the outer skin and maintaining the aesthetic appearance of the skin or fur, i.e. despite high concentrations of active substances. Ensure there is no tendency to stick or sticky appearance.
The formulation can also include an antioxidant intended to prevent oxidation in air, the material comprising from about 0.005 to about 1% (w / v), and from about 0.01 to about 0.05% ( It exists at a rate selected from the range consisting of w / v).
In one embodiment of the antioxidant, this material is conventional in the art, butylated hydroxyanisole, butylated hydroxytoluene, ascorbic acid, sodium metabisulfite, propyl gallate, sodium thiosulfate or many of these A mixture of the two, but is not limited thereto.
Formulation aids are well known to those skilled in the art and can be obtained commercially or obtained by known techniques. These concentrated compositions are generally prepared by simply mixing the ingredients defined above. Advantageously, the starting point is to mix the active substance with the main solvent and then add other ingredients or adjuvants.

The applied volume can be about 0.3 to about 1 ml. In one embodiment of the volume, the volume is about 0.5 ml for cats and about 0.3 to about 3 ml for dogs, depending on the mass of the animal.
In other embodiments of the present invention, the application of the spot-on formulation of the present invention can also provide a sustained and wide range of efficacy when the solution is applied to mammals or birds. Spot-on formulations topically administer concentrated solutions, suspensions, microemulsions or emulsions for application intermittently between animal spots, usually between both shoulders (spot-on type solutions).
For spot-on formulations, the carrier can be a liquid carrier excipient as described in US Pat. No. 6,426,333, wherein one embodiment of the spot-on formulation includes a solvent and a co-solvent, Solvents are acetone, acetonitrile, benzyl alcohol, butyl diglycol, dimethylacetamide, dimethylformamide, dipropylene glycol n-butyl ether, ethanol, isopropanol, methanol, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, monomethylacetamide, dipropylene glycol Monomethyl ether, liquid polyoxyethylene glycol, propylene glycol, 2-pyrrolidone (for example, N-methylpyrrolidone), diethylene glycol monoethyl ether, ethylene glycol, di- Chirufutareto fatty acid esters, such as diethyl ester or diisobutyl adipate, and selected from the group consisting of a mixture of at least two of these solvents, co-solvents are selected from the group consisting of absolute ethanol, isopropanol or methanol.
Liquid carrier excipient is optionally anionic surfactant, cationic surfactant, nonionic surfactant, amine salt, amphoteric surfactant or polyvinylpyrrolidone, polyvinyl alcohol, copolymer of vinyl acetate and vinylpyrrolidone, polyethylene glycol A crystallization inhibitor selected from the group consisting of benzyl alcohol, mannitol, glycerol, sorbitol, polyoxyethylenated sorbitan ester, lecithin, sodium carboxymethylcellulose, and acrylic acid derivatives, or a mixture of these crystallization inhibitors be able to.

A spot-on formulation can be prepared by dissolving the active ingredient in a pharmaceutically or veterinary acceptable excipient. Alternatively, a spot-on formulation can be prepared by encapsulating the active ingredient such that the therapeutic agent remains on the surface of the animal. These formulations will vary the mass of the therapeutic agent in combination depending on the species of host animal to be treated, the severity and type of infection and the weight of the host.
In one embodiment of the invention, the active agent is present in the formulation at a concentration of about 0.05 to 10 mass / volume%. In another embodiment of the invention, the active agent is present in the formulation at a concentration of about 0.1-2% w / v. In yet another embodiment of the present invention, the active agent is present in the formulation at a concentration of about 0.25 to about 1.5 mass / volume%. In yet another embodiment of the invention, the active agent is present in the formulation at a concentration of about 1% weight / volume.
Compositions containing the active agents of the invention can be administered sequentially for treatment or prevention by known methods. In general, a dose of about 0.001 to about 100 mg / kg body weight of active agent administered as a single dose or in divided doses for 1 to 5 days will be satisfactory, but a higher or lower dose range is required Of course, such dosages are also within the scope of the present invention. Determining specific dosing regimens for individual hosts and parasites is well within the ordinary skill of those in the art.
In other embodiments, the treatment is by direct topical administration, such as a paste, pour-on, ready-to-use, spot-on type formulation. Larger amounts can be released in or on the animal's body for a very long time.
In other embodiments, the amount of active ingredient for birds and small animals is greater than about 0.01 mg / kg, and in other embodiments for the treatment of small size birds and animals, the amount of active agent is about 1 to about 100 mg / kg animal body weight.

In one embodiment, the direct pour-on transdermal formulation of the present invention can provide sustained and wide range of efficacy when the solution is applied to one or more points along the back of the animal, eg, the line of the back. . According to a first embodiment in which the pour-on formulation is administered directly, the method comprises applying the solution to an animal, the application being repeated every month or every two months. According to a second embodiment in which the pour-on formulation is administered directly, it includes a method of applying the solution to livestock animals before arriving at the feed site, which can be the last application before slaughtering the animals It is. It is clear that the method can also consist of combining these two embodiments, ie the first embodiment followed by the second embodiment.
The solution of the present invention may be applied using any means known per se, for example using an application gun or a measuring flask.
The method serves to clean the animal's skin and hair by eliminating not only the parasites on it but also their remnants and excrement. As a result, the animal no longer feels stress due to the parasite or its stings, which is a positive result for its growth and use of food supply, for example.
In other embodiments, the compounds of the invention are administered in spot-on formulations. The application of the spot-on formulation of the present invention can also provide a sustained and wide range of efficacy when the solution is applied to mammals or birds. Administration of the spot-on formulation may be intermittent in time and may be administered daily, weekly, biweekly, monthly, bimonthly or seasonally, or even longer. The time between treatments depends on factors such as the parasite being treated, the degree of invasion, the type of mammal or bird and the environment in which it lives. It is well within the level of skill of those skilled in the art to determine the individual dosing period for a particular situation. The present invention contemplates a method of permanently eradicating parasites in an environment where the animal is subjected to strong parasitic pressures, where administration is much less frequent than daily administration. For example, it is preferred that the treatment of the present invention be performed monthly in dogs and cats.

Without wishing to be bound by theory, it is believed that these formulations work by dissolving the dose in the natural sebum of the host's skin, fur or feathers. From there, the active agent distributes through the sebaceous glands of the skin and into the host's body. The therapeutic agent is also left in the sebaceous glands. Thus, the gland provides a natural reservoir for the active agent that allows the substance to be drained back into the vesicles for reapplying itself to the skin and hair. This in turn eliminates the need to re-administer the dose after the host has become wet due to rain or bathing, etc., as well as a longer period between applications. The formulations of the present invention further allow the grooming animal to take the therapeutic agent orally, thereby becoming ill or possibly interacting with other therapeutic agents that are administered orally. Has the advantage of not sticking directly to the fur.
Administration of spot-on formulations also provides a method of cleaning the skin and skin of animals by removing existing parasites and their waste and excreta. Thus, the treated animals show an outer skin that is more pleasing in appearance and feels better to the touch.
In one embodiment of the location of administration, a single formulation in a form that contains the active agent in a substantially liquid carrier and allows for one or a few repeated applications is provided to the animal. Will be administered over a local area of, for example, between both types. In one embodiment of the invention, the local region has a surface area of about 10 cm ² or greater. In other embodiments of the invention, the local region has a surface area of about 5 to about 10 cm ² .
Other administration routes include paste formulations, oral drench formulations, chewable formulations, transdermal or transmucosal patches or liquids, gels or pastes, inhalation solutions and injectable formulations.
Additional active ingredients can also be included in the compositions of the present invention.

These additional active agents include, but are not limited to, acaricides, anthelmintics, antiparasitic agents (both endoparasites and ectoparasites) and pesticides. It may be added. Substances known in the art that can be used in the composition (e.g., Plumb 'Veterinary Drug Handbook, 5 ^th Edition, ed. Donald C. Plumb, Blackwell Publishing, (2005) or The Merck Veterinary Manual, 9 ^th Edition, (See January 2005). Albuterol, alfentanil HCl, allopurinol, alprazolam, altrenogest, amantadine HCl, amikacin sulfate, aminocaproic acid, aminopentamide hydrogen sulfate, aminophylline / theophylline, amiodarone HCl, amitraz, amitriptyline HCl, amlodipine besylate Ammonium chloride, ammonium molybdate, amoxicillin, amoxicillin, potassium clavulanate, amphotericin B desoxycholate, amphotericin B lipid base, ampicillin, amprolium HCl, antacid (oral), antitoxin, apomorphine HCl, apramycin sulfate, ascorbic acid , Asparaginase, aspirin, atenolol, atipamezole HCl, atracurium besylate, atropine sulfate, auranofin, aurothioglucose, azaperone, azathioprine, azithromycin, baclofen, barbituric acid hypnotics, benazepril HCl, betamethasone, betanecol chloride, bisacodyl Bismuth subsalicylate, bleomycin sulfate,

Boldenone undecylenate, bromide, bromocriptine mesylate, budenoside, buprenorphine HCl, buspirone HCl, busulfan, butorphanol tartrate, cabergoline, salmon calcitonin, calcitrol, calcium salts, captopril, carbenicillin indanyl sodium, carbimazole, carboplatin, carnitol, carnitol , Cefadroxyl, cefazolin sodium, cefixime, cefoperazone sodium, cefotaxime sodium, cefotetan disodium, cefoxitin sodium, cefpodoxime proxetyl, ceftazidime, ceftiofur sodium, ceftiofur HCl, ceftriaxone sodium, cephalexin, cephalo Sporin, cefapirin, charcoal (activated carbon), Rambucil, chloramphenicol, chlordiazepoxide, chlordiazepoxide +/- clidinium bromide, chlorothiazide, chlorpheniramine maleate, chlorpromazine HCl, chlorpropamide, chlortetracycline, chorionic gonadotropin (HCG), chromium, cimetidine, ciprofloxy Sasin, cisapride, cisplatin, citrate, clarithromycin, clemastine fumarate, clenbuterol HCl, clindamyce, clofazimine, clomipramine HCl, clonazepam, clonidine, cloprostenol sodium, dipotassium chlorazepate, chlorthrone, cloxacillin, codeine phosphate, Colchicine, corticotropin (ACTH), cosyntropin, cyclophosphamide, cyclosporine, cyproheptadine HCl, cytarabine, da Carbazine, dactinomycin / actinomycin D, dalteparin sodium, danazol, dantrolene sodium, dapsone, decoquinate, deferoxamine mesylate, deracoxib, deslorelin acetate, desmopressin acetate, dezoxycorticosterone pivalate,

Detomidine HCl, dexamethasone, dexpantenol, dexrazoxane, dextran, diazepam, diazoxide (oral), diclofenamide, dichlorvos, diclofenac sodium, dicloxacillin, diethylcarbamazine citrate, diethylstilbestrol (DES), difloxacin HCl, digoxin, dihydrotaxy Sterol (DHT), diltiazem HCl, dimenhydrinate, dimercaprol / BAL, dimethyl sulfoxide, dinoprostromethamine, diphenylhydramine HCl, disopyramide phosphate, dobutamine HCl, docusate / DSS, dolacetron mesylate, domperidone, dopamine HCl, doramectin, doxapram HCl, doxepin HCl, doxorubicin HCl, doxycycline, calcium disodium edetate, calcium EDTA, salt Edrophonium, enalapril / enalaprilate, enoxaparin sodium, enrofloxacin, ephedrine sulfate, epinephrine, epoetin / erythropoietin, eprinomectin, epsiprantel, erythromycin, esmolol HCl, estradiol cypriate, ethacrynic acid / ethroic acid sodium ethanol (alcohol) , Etodolac, etomidate, euthanasia w / pentobarbital, famotidine, fatty acid (essential / omega), ferbamate, fenbendazole, fentanyl, ferrous sulfate, filgrastim, finasteri, fipronil, florfenicol, fluconazole, flucytosine , Fludrocortisone acetate, flumazenil, flumethasone, flunixin meglumine, fluo Uracil (5-FU), fluoxetine, fluticasone propionate, fluvoxamine maleate, fomepizole (4-MP), furazolidone, furosemide, gabapentin, gemcitabine HCL, gentamicin sulfate, glimepiride, glipizide, glucagon, glucocorticoid agent, glucosamine / chondroitin sulfate , Glutamine, glyburide, glycerin (oral), glycopyrrolate, gonadorelin, griseofulvin, guaifenesin, halothane, hemoglobin tamer-200 (oxyglobin (registered trademark)), heparin, hetastarch, sodium hyaluronate, hydrazarin HCl, hydrochlorothiazide, hydrocodone tartaric acid Hydrogen salt, hydrocortisone, hydromorphone, hydroxyurea,

Hydroxidine, ifosfamide, imidacloprid, imidocarb dipropionate, impenem-cilastatin sodium, imipramine, inamrinone lactate, insulin, interferon alfa-2a (human recombinant), iodide (sodium / potassium), tocone (syrup), ipodate Sodium, dextran iron, isoflurane, isoproterenol HCl, isotretinoin, isoxsuprine HCl, itraconazole, ivermectin, kaolin / pectin, ketamine HCl, ketoconazole, ketoprofen, ketorolac tromethamine, lactulose, leuprolide, levamisole, levetiracetam, levothiroxine, Lidocaine HCl, lincomycin HCl, liothyronine sodium, lisinopril, lomustine (CCNU), lufenuron, ricin , Magnesium, mannitol, marvofloxacin, mechlorethamine HCl, meclizine HCl, meclofenamic acid, medetomidine HCl, medium chain triglyceride, medroxyprogesterone acetate, megestrol acetate, melarsomine, melatonin, meloxicam, melphalan, meperidine HCl, mercaptopurine , Meropenem, metformin HCl, methadone HCl, tazolamide, methenamine mandelate / hippurate, methimazole, methionine, metcarbamol, methotexal sodium, methotrexate, methoxyflurane, methylene blue, methylphenidate, methylprednisolone, metoclopramide HCl, metoprolol , Metronidazole, mexiletine HCl, mibolerone, midazolam HCl milbemycin oxime, mineral oil, minocycline HCl, mi Prostol, mitotane, mitoxantrone HCl, morantel tartrate, morphine sulfate, moxidectin, naloxone HCl, nandrolone decanoate, naproxen, narcotic (opiate) agonist analgesic, neomycin sulfate, neostigmine, niacinamide, nitazoxanide, nitenpyram, nitrofuranto In, nitroglycerin, sodium nitroprusside, nizatidine, novobiocin sodium, nystatin, octreotide acetate, olsalazine sodium, omeprazole, ondansetron, narcotic antidiarrheal agent,

Orbifloxacin, oxacillin sodium, oxazepam, oxfendazole, oxybutynin chloride, oxymorphone HCl, oxytetracycline, oxytocin, disodium pamidronate, pancrelipase, pancuronium bromide, paromomycin sulfate, paroxetine HCl, penicillamine, Penicillins, penicillin G, penicillin V potassium, pentazocine, pentobarbital sodium, pentosan polysulfate, pentoxyphyllin, pergolide mesylate, phenobarbital, phenoxybenzamine HCl, phenylbutazone, phenylephrine HCl, phenylpropanolamine HCl, Phenytoin sodium, pheromone, parenteral phosphate, phytonadione / vitamin K-1, pimobendan, piperazine, pillli Mycin HCl, piroxicam, polysulfated glycosaminoglycan, ponazuryl, potassium chloride, pralidoxime chloride, praziquantel, prazosin HCl, prednisolone / prednisone, primidone, procainamide HCl, procarbazine HCl, prochlorperazine, propantherine bromide, pro Pionibacterium acnes injection, propofol, propranolol HCl, protamine sulfate, pseudoephedrine HCl, psyllium hydrophilic mucilage, pyrantel pamoate, pyridostigmine bromide, pyriramine maleate, pyrimethamine, quinacrine HCl, quinidine, ranitidine HCl, rifampin, s- Adenosylmethionine (SAMe), saline / osmotic laxative, selamectin, selegiline HCl / 1-deprenyl, sertraline HCl, sevelamer HCl, sevoflurane, silymarin / o Thistle, sodium bicarbonate, polystyrene sodium sulfate, sodium stibogluconate, sodium sulfate, sodium thiosulfate, somatotropin, sotalol HCl, spectinomycin HCl, spironolactone, stanozolol, streptokinase, streptozocin, saccimer, succinylcholine chloride, sucralfate,

Sufentanyl citrate, sulfachlorpyridazine sodium, sulfadiazine / trimethoprim, sulfamethoxazole / trimethoprim, sulfadimethoxine, sulfadimethoxine / olmethoprim, sulfasalazine, taurine, tepoxaline, terbinafine HCl, terbutaline sulfate, testosterone, tetracycline HCl, thiabenzol thiol Arsamide sodium, thiamine HCl, thioguanine, thiopental sodium, thiotepa, thyrotropin, thiamulin, ticarcillin disodium, thiretamine HCl / zolazepam HCl, tilmicosin, thiopronin, tobramycin sulfate, tocainide HCl, trazoline HCl, terfenamic acid, topiramate, tramadol HCl, triamcinolone acetonide, trientine HCl, trilostane, trimeprazine tartrate w / prednisolone, tripelenamine HCl, tylosin, ursodiol, valproic acid, vanadium, vancomycin HCl, vasopressin, vecuronium bromide, verapamil HCl, vinblastine sulfate, vincristine sulfate, vitamin E / selenium, warfarin sodium, xylazine Examples include, but are not limited to, HCl, yohimbine HCl, zafirlukast, zidovudine (AZT), zinc acetate / zinc sulfate, zonisamide and mixtures thereof.

In one embodiment of the invention, other arylpyrazole compounds such as phenylpyrazole in the above background art (e.g., fipronil) are known in the art and suitable for use with the dimeric arylpyrazole compounds of the invention. ing. Examples of such arylpyrazole compounds include U.S. Pat.Nos. 6,001,384; 6,010,710; 6,083,519; 6,096,329; 6,174,540; 6,685,954. And those described in US Pat. No. 6,998,131 (assigned to Merial, Ltd., Duluth, GA, respectively), but are not limited thereto.
In another embodiment of the present invention, nozurisporic acid and its derivatives (known types of acaricides, anthelmintics, antiparasitic agents and insecticides) can be added to the compositions of the present invention. These compounds are used to treat or prevent infections in humans and animals and are described, for example, in US Pat. Nos. 5,399,582 and 5,962,499. The composition can include one or more of nozurisporic acid and its derivatives known in the art, including all stereoisomers, such as those described in the references cited above.
In other embodiments of the present invention, one or more macrocyclic lactones that act as acaricides, anthelmintics and insecticides can be added to the compositions of the present invention.
Macrocyclic lactones include, but are not limited to, avermectins such as abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, and rubemycin, such as milbemectin, milbemycin D, moxidectin, and nemadectin. Also included are 5-oxo derivatives and 5-oxime derivatives of the avermectin and rubemycin. Examples of combinations of arylpyrazole compounds and macrocyclic lactones include U.S. Patent Nos. 6,426,333, 6,482,425, 6,962,713, and 6,998,131 (Merial, Ltd. Including, but not limited to, those described in Duluth, GA).

Macrocyclic lactones are natural products or semi-synthetic derivatives thereof. The structures of avermectin and milbemycin are closely related, for example, by sharing a complex 16-membered macrocyclic lactone ring. The natural product avermectin is disclosed in US Pat. No. 4,310,519, and the 22,23-dihydroavermectin compound is disclosed in US Pat. No. 4,199,569. In particular, U.S. Pat.Nos. 4,468,390, 5,824,653, European Patent Application Publication No. 0 007 812 A1, British Patent No. 1 390 336, European Patent No. 0 002 916 and There is also New Zealand Patent No. 237 086. Naturally occurring milbemycin is variously cited in US Pat. No. 3,950,360, “The Merck Index” 12 ^th ed., S. Budavari, Ed., Merck & Co., Inc. Whitehouse Station, New Jersey (1996). In the literature. Semisynthetic derivatives of these types of compounds are well known in the art, for example, U.S. Pat.Nos. 5,077,308, 4,859,657, 4,963,582, 4,855,317, No. 4,871,719, No. 4,874,749, No. 4,427,663, No. 4,310,519, No. 4,199,569, No. 5,055,596, No. 4,973,711, No. Nos. 4,978,677, 4,920,148, and EP 0 667 054.
In other embodiments of the present invention, a type of acaricide or insecticide known as an insect growth regulator (IGR) can also be added to the compositions of the present invention. Compounds belonging to this group are well known to those skilled in the art and exhibit a wide variety of different chemical types. All these compounds act by interfering with the development or growth of pests. Examples of insect growth regulators include, for example, U.S. Pat.Nos. 3,748,356, 3,818,047, 4,225,598, 4,798,837, 4,751,225, and European Patent 0 179. No. 022 or British Patent No. 2 140 010 and U.S. Pat.Nos. 6,096,329 and 6,685,954, both assigned to Merial Ltd., Duluth, GA . Examples of IGRs suitable for use include metoprene, pyriproxyfen, hydroprene, cyromazine, fluazuron, lufenuron, nobarulone, pyrethroid, formamidine and 1- (2,6-difluorobenzoyl) -3- (2-fluoro- 4- (Trifluoromethyl) phenylurea may be mentioned but not limited thereto.

Anthelmintic agents that can be combined with the compounds of the present invention to form compositions include benzene disulfonamide compounds, including but not limited to chlorthrone; or stripworm control including but not limited to praziquantel, pyrantel or morantel It can be an agent.
Anti-parasitic agents that can be combined with the compounds of the present invention to act on neuromuscular junctions by stimulating presynaptic receptors belonging to the secretin receptor family, causing parasite paralysis and death Can be a biologically active peptide or protein including, but not limited to, depsipeptides. In one embodiment of a depsipeptide, the depsipeptide is emodepside.
An insecticide that can be combined with the compounds of the present invention to form a composition can be a substituted pyridylmethyl derivative compound such as spinosyn (eg, spinosad) or imidacloprid. This type of agent is described above, for example, in US Pat. No. 4,742,060 or EP 0 892 060. It will be sufficient within the level of ordinary skill in the art to determine which individual compounds can be used in the formulations of the present invention to treat specific insect infections.
In other embodiments, the compositions of the present invention may advantageously include one or more compounds of the compound isoxazolines. These active agents are disclosed in International Publication No. 2007/079162, Pamphlet No. 2007/075459, US Patent Application Publication No. 2009/0133319, International Publication No. 2007/070606 Pamphlet, and US Patent Application Publication No. 2009. / 0143410 specification, WO 2009/003075 pamphlet, 2009/002809 pamphlet, 2009/024541 pamphlet, 2005/085216 pamphlet, US Patent Application Publication No. 2007/0066617 pamphlet, It is described in the pamphlet of International Publication No. 2008/122375, and all the descriptions of these specifications are included in this specification as a whole.

In another embodiment of the present invention, nozurisporic acid and its derivatives (known acaricides, anthelmintics, antiparasitic agents, insecticide types) may be added to the compositions of the present invention. These compounds are used to treat or prevent infection in humans and animals, e.g., U.S. Patent Nos. 5,399,582, 5,962,499, 6,221,894, 6,399,786. All the descriptions of these specifications are included in the present specification as a whole. The composition may include one or more of the nozurisporic acid derivatives known in the art, including all stereoisomers, such as those described in the literature cited above.
In another embodiment, aminoacetonitriles (AAD) anthelmintic compounds such as monepantel (ZOLVIX) may be added to the compositions of the present invention. These compounds are described, for example, in WO 2004/024704; Sager et al., Veterinary Parasitology, 2009, 159, 49-54; Kaminsky et al., Nature vol. 452, 13 March 2008, 176-181. be written.
The compositions of the present invention also include those described in Soll et al, U.S. Patent Application Publication No. 2008/0312272, the description of which is incorporated herein in its entirety. Aryloazol-2-ylcyanoethylamino compound, and U.S. Patent Application Publication No. 12 / 582,486, filed October 20, 2009, the description of which is incorporated herein in its entirety. Thioamide derivatives of these compounds described in

The compositions of the present invention can also be combined with paraherkamide compounds, including derquantel, and derivatives of these compounds (Ostlind et al., Research in Veterinary Science, 1990, 48, 260-61; and Ostlind et al. al., Medical and Veterinary Entomology, 1997, 11, 407-408). The parahelkamide family of compounds is a known class of compounds containing a spirodioxepinoindole core that is active against certain parasites (Tet. Lett. 1981, 22, 135; J. Antibiotics 1990 , 43, 1380, J. Antibiotics 1991, 44, 492). Furthermore, the structurally related marcfortine family of compounds, for example marcfortine AC, is also known and may be combined with the formulations of the present invention (J. Chem. Soc.-Chem. Comm. 1980, 601, Tet. Lett. 1981, 22, 1977). Further, for the paraherkamide derivative, for example, WO 91/09961, pamphlet 92/22555, pamphlet 97/03988, pamphlet 01/076370, pamphlet 09/004432, U.S. Pat. No. 5,703,078, U.S. Pat. No. 5,750,695, all of which are hereby incorporated by reference in their entirety.
In general, the additional active agent is included at a dosage of about 0.1 μg to about 1000 mg. More typically, the additional active agent may be included at a dosage of about 10 μg to about 500 mg, about 1 mg to about 300 mg, about 10 mg to about 200 mg, or about 10 mg to about 100 mg. In one embodiment of the invention, the additional active agent is included at a dosage of about 1 g to about 10 mg. In other embodiments of the invention, the additional active agent may be included at a dosage of animal body weight of about 5 μg / kg to about 50 mg / kg. In other embodiments, the additional active agent is from about 0.01 mg / kg to about 30 mg / kg, from about 0.1 mg / kg to about 20 mg / kg, or from about 0.1 mg / kg to about 10 mg / kg of animal weight. It may be present at a dosage. In other embodiments, the additional active agent may be present at a dosage of animal body weight of about 5 μg / kg to about 200 g / kg or about 0.1 mg / kg to about 1 mg / kg. In yet another embodiment of the invention, the additional active agent is included at a dosage of about 0.5 mg / kg to about 50 mg / kg.
The weight ratio of dimeric arylpyrazole compound to additional insecticide is, for example, from about 5/1 to about 10,000 / 1. However, one of ordinary skill in the art will be able to select the ratio of dimeric arylpyrazole compound and additional insecticide that is appropriate for the intended host and its use.

The compound of the present invention or a salt thereof alone or other insecticidally active substance, such as insecticide, attractant, fungicide, acaricide, nematicide, herbicide, fungicide, It can be used in the form of a preparation (formulation) in combination with safeners, fertilizers and / or growth regulators, for example as a premix / ready mix.
Classification of fungicides is well known in the art and includes classification by the FRAC (Agricultural Resistant Behavioral Committee). Fungicides that may be mixed if necessary include methyl benzimidar carbamates such as benzimidar, thiophanate; dicarboximide; demethylation inhibitors such as imidazole, piperazine, pyridine, pyrimidine, triazole; phenyl Amides such as acylalanine, oxazolidinone, butyrolactone; amines such as morpholine, piperidine, spiroketal amines; phosphorothiolates; dithiolanes; carboxamides; hydroxy- (2-amino-) pyrimidines; anilinopyrimidines; N-phenylcarbamates Quinone external inhibitor; phenylpyrrole; quinoline; aromatic hydrocarbon; heteroaromatic compound; melanin biosynthesis inhibitor-reductase; melanin biosynthesis inhibitor-dehydratase; hydroxyanilide (SBI class III), eg Phenhexamide; SBI class IV, for example, thiocarbamate, allylamine; polyoxin; phenylurea; quinone internal inhibitor; benzamide; enopyranuronic acid antibiotics; hexopyranosyl antibiotics; glucopyranosyl antibiotics; glucopyranosyl antibiotics; Carbamate; Uncoupler of oxidative phosphorylation; Organotin compound; Carboxylic acid; Heteroaromatic compound; Phosphonate; Phthalamic acid; Benzotriazine; Benzenesulfonamide; Pyridazinone; Carboxylic acid amide; Tetracycline antibiotic; Thiocarbamate; Benzothiadiazole BTH; benzisothiazole; thiadiazole carboxamide; thiazole carboxamide; benzamidoxime; quinazolinone; benzophenone; acyl picoride; inorganic compound For example, copper salts, sulfur, dithiocarbamates and analogs; phthalimido; chloronitrile; sulfamide; guanidine; triazine; quinone but are not limited thereto. Other fungicides that may be optionally mixed may also be from the types of compounds described in US Pat. Nos. 7,001,903 and 7,420,062.

  Herbicides known from the literature and classified by HRAC (Herbicide Resistance Task Force) and which can be combined with the compounds of the present invention include, for example: aryloxyphenoxypropionate; cyclohexanedione; phenylpyrazoline; sulfonylurea Imidazolinones, such as imazapic, imidazole; triazolopyrimidines; pyrimidinyl (thio) benzoates; sulfonylaminocarbonyltriazolinones; triazines, such as atrazine; triazinones; triazolinones; uracils; pyridazinones; phenylcarbamates; ureas; nitriles; Benzothiadiazinone; phenylpyridazine; bipyridylium, for example, paraquat; diphenyl ether; phenylpyrazole; N-phenylphthalimide; thiadiazole; thiadiazole; triazolino Oxazolidinedione; Pyrimidinedione; Pyridazinone; Pyridinecarboxamide; Triketone; Isoxazole; Pyrazole; Triazole; Isoxazolidinone; Urea, eg, Linuron; Diphenyl ether; Glycine, eg, glyphosate; Phosphinic acid, eg, glufosinate ammonium; Carbamate; dinitroaniline such as pendimethalin; phosphoramidate; pyridine; benzamide; benzoic acid; chloroacetamide; metolachlor; acetamide; oxyacetamide; tetrazolinone; nitrile; benzamide; triazolocarboxamide; quinolinecarboxylic acid; dinitrophenol; Phosphorodithioate; benzofuran; chlorocarbonic acid; phenoxycarboxylic acid, eg 2,4-D; benzoic acid, eg di Pyridine carboxylic acid such as clopyralide, triclopyr, fluroxypyr, picloram; quinoline carboxylic acid; phthalamate semicarbazone; arylaminopropionic acid; arylaminopropionic acid; organic arsenic compound. Other herbicides that may be optionally mixed are the compounds described in US Pat. Nos. 7,432,226, 7,012,041, and 7,365,082. Suitable herbicide safeners include benoxacol, croquintoset, ciomethrinyl, cyprosulfamide, dichlormide, dicyclonone, dietolate, fenchlorazole, fenchlorim, flurazole, floxophenim, flirazole, isoxadifen, mefenpyr, mephenate, naphthalic anhydride And oxabetalinyl, but are not limited to these.

Bactericides include but are not limited to bronopol, dichlorophen, nitrapirine, nickel dimethyldithiocarbamate, kasugamishi, octirinone, furancarboxylic acid, oxytetracycline, probenazole, streptomycin, teclophthalam, copper sulfate and other copper preparations. .
Insecticides / acaricides / nematicides are described in U.S. Pat.Nos. 7,420,062, 7,001,903, U.S. Patent Application Publication No. And compounds classified by IRAC (Insecticide Resistance Committee). Examples of insecticide / acaricide / nematicide include carbamate; triazemate; organophosphate; cyclodiene organochlorine; phenylpyrazole; DDT; methoxychlor; pyrethroid; pyrethrin; neonicotinoid; nicotine; Hydroxyl; Nereistoxin analog; Spinosyn; Avermectin and milbemycin; Juvenile hormone-like substance; Alkyl; Chloropicrin; Sulfuryl fluoride; Cryolite; Pymetrozine; Flonicamid; Clofentezine; Hexithiazox; Etoxazole; ); Diafenthiuron; organotin tick control agent; propargite; tetradiphone; chlorfenapyr; DNOC; benzoylurea; buprofezin; cyromazine; diacylhydrazine; azadirachtin; amitraz; hydrame Tilnon; acequinosyl; fluacrylpyrim; METI acaricide; rotenone; indoxacarb; metaflumizone; tetronic acid derivatives; aluminum phosphide; cyanide; phosphine; biphenazate; fluoroacetate; P450-dependent monooxygenase inhibitor; esterase inhibitor; diamide; benzo Ximethionate; quinomethionate; dicohol; pyridalyl; borax; talcumite; fumigant such as, but not limited to, methyl bromide;

The compounds of the invention can be formulated in various ways depending on the predominant biological and / or physicochemical parameters. Examples of possible formulations are: wettable powder (WP), water-soluble powder (SP), water-soluble concentrate, emulsifiable concentrate (EC), emulsions such as oil-in-water emulsions and water-in-oil emulsions (EW ), Sprayable liquid, suspension concentrate (SC), oil or water based dispersion, oil miscible liquid, capsule suspension (CS), dust (DP), seed dressing formulation, wide area Granules for spraying and soil treatment, fine granules, spray granules, coated granules, granules in the form of adsorption granules (GR), water-dispersible granules (WG), water-soluble granules (SG), ULV formulations, Microcapsules and waxes.
The above-mentioned preparations are prepared in a known manner, for example, the active compound and at least one solvent or diluent, emulsifier, dispersant and / or binder or fixative, water repellent, and optionally a desiccant, UV-stable. It can be prepared by mixing with one or more of agents, colorants, pigments, and other processing aids.
These individual formulation types are known in principle, for example: Winnacker-Kuechler, "Chemische Technologie" [Chemical Technology], Volume 7, C. Hauser Verlag, Munich, 4th Edition 1986; Wade van Valkenburg, "Pesticide Formulations ", Marcel Dekker, NY, 1973; K. Martens," Spray Drying Handbook ", 3rd Ed. 1979, G. Goodwin Ltd. London.
Necessary formulation aids such as inert substances, surfactants, solvents, other additives are also known, eg: Watkins, "Handbook of Insecticide Dust Diluents and Carriers", 2nd Ed., Darland Books, Caldwell NJ; Hv Olphen, "Introduction to Clay Colloid Chemistry", 2nd Ed., J. Wiley & Sons, NY; C. Marsden, "Solvents Guide", 2nd Ed., Interscience, NY 1963; McCutcheon's "Detergents and Emulsifiers Annual" , MC Publ. Corp., Ridgewood NJ; Sisley and Wood, "Encyclopedia of Surface Active Agents", Chem. Publ. Co. Inc., NY 1964; Schoenfeldt, "Grenzflaechenaktive Aethylenoxidaddukte" [Surface-active ethylene oxide adducts], Wiss Verlagsgesell., Stuttgart 1976; Winnacker-Kuechler, "Chemische Technologie" [Chemical Technology], Volume 7, C. Hauser Verlag, Munich, 4th Ed. 1986.

Wetting powders are uniformly dispersed in water and, in addition to the compounds of the invention, ionic and / or nonionic surfactants (wetting agents, dispersing agents) such as polyoxyethylated alkylphenols, polyoxyethyls Fatty alcohol, polyoxyethylated aliphatic amine, fatty alcohol polyglycol ether sulfate, alkane sulfonate or alkylbenzene sulfonate, sodium lignin sulfonate, 2,2'-dinaphthylmethane-6,6'-sodium disulfonate, dibutyl It is a preparation containing sodium naphthalenesulfonate or sodium oleylmethyl taurate in addition to a diluent or an inert substance. In order to prepare a wettable powder, the compounds of the invention are finely ground in a conventional apparatus such as, for example, a hammer mill, blower mill, air jet mill, and mixed with a compounding aid at the same time or thereafter.
Emulsifiable concentrates, for example, convert a compound of the present invention into one or more ionic and organic solvents such as butanol, cyclohexanone, dimethylformamide, xylene or higher boiling aromatic compounds or hydrocarbons or mixtures thereof. It is prepared by adding and / or dissolving a nonionic surfactant (emulsifier). Emulsifiers that can be used are, for example, calcium salts of alkylaryl sulfonic acids such as calcium dodecylbenzene sulfonate, or fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide / ethylene oxide condensates, alkyls. Nonionic emulsifiers such as polyethers, sorbitan esters such as sorbitan fatty acid esters, or polyoxyethylene sorbitan esters such as polyoxyethylene sorbitan fatty acid esters.
The dusting agent is obtained by grinding the active substance with a finely ground solid material, such as talc or natural clay, such as kaolin, bentonite or pyrophyllite, or diatomaceous earth.

The suspension concentrate can be water or oil based. These can be prepared, for example, by commercially available bead mills, for example in the case of other formulation types, as already mentioned, with the addition of surfactants where appropriate and wet milling.
Emulsions, such as oil-in-water emulsions (EW), can be prepared using aqueous organic solvents and, where appropriate, for example, surfactants already mentioned in the case of other formulation types, stirrers, colloid mills and / or Alternatively, it can be prepared by a static mixer.
Granules are prepared by spraying the compounds of the invention onto adsorbent particulate inert materials or by binding active substance concentrates such as sand, kaolinite with binders such as polyvinyl alcohol, sodium polyacrylate or mineral oil. It can be prepared by applying on the surface of a carrier or particulate inert material. Suitable active substances can also be granulated in a manner customary for the production of fertilizer granules, if desired in admixture with fertilizers.
Water dispersible granules are typically prepared by conventional methods such as spray drying, fluid bed granulation, disk granulation, mixing in a high speed mixer, extrusion without solid inert material. To prepare disc granules, fluid bed granules, extruded granules, spray granules, for example, "Spray-Drying Handbook" 3rd ed. 1979, G. Goodwin Ltd., London; JE Browning, "Agglomeration", Chemical and Engineering 1967, pages 147 et seq .; "Perry's Chemical Engineer's Handbook", 5th Ed., McGraw-Hill, New York 1973, p. 8-57.
Generally, the agrochemical formulation comprises a range of compounds of the present invention selected from the group consisting of about 0.1 to about 99% by weight and about 0.1 to about 95% by weight.

The concentration of the compound of the present invention in the wet powder is, for example, from about 10 to about 90% by weight, with the remainder up to 100% by weight being composed of conventional formulation ingredients. In the case of an emulsifiable concentrate, the concentration of the compound of the present invention can be in a range selected from the group consisting of about 1% to about 90% by weight and about 5% to about 80% by weight. Formulations in the form of dust usually comprise a range of compounds of the present invention selected from the group consisting of about 1% to about 30%, and about 5% to about 20% by weight. Sprayable solutions comprise a range of compounds of the invention selected from the group consisting of about 0.05% to about 80% by weight, and about 2% to about 50% by weight. In the case of a water-dispersible granule, the content of the compound of the present invention depends in part on whether the compound of the present invention is liquid or solid, and the use of a granulating aid, filler or the like. The water-dispersible granule includes, for example, a range selected from the group consisting of about 1 to about 95% by mass and about 10% to about 80% by mass.
In addition, formulations of the compounds of the present invention may be formulated as appropriate with adhesives, wetting agents, dispersants, emulsifiers, penetrants, preservatives, antifreeze agents, solvents, fillers, carriers, colorants, antifoams. Agents, evaporation inhibitors, pH modifiers and viscosity modifiers, which are conventional in any case.
The mixtures according to the invention can be applied via soil before germination or after germination. The mixtures according to the invention can also be applied via leaves. The mixture of the present invention can be used for seed dressing. It is also possible to apply the mixtures according to the invention via an irrigation system, for example via irrigation water.
When used as insecticides, the active compounds according to the invention can furthermore be present in the commercial preparations and in the use forms prepared from these preparations, as a mixture with synergists. A synergist is a compound that increases the action of the active compound, and the added synergist need not be active per se.
When used as insecticides, the active compounds according to the invention are furthermore used in their commercial formulations and in the use forms prepared from these formulations, in the plant environment, on the surface of plant parts or in plant tissues. Can be present as a mixture with an inhibitor that reduces degradation of the active compound.

The active compound content of the use forms prepared from commercial preparations can vary within wide limits. The active compound concentration of the use forms can be from about 0.00000001 to about 95% by weight, preferably from about 0.00001 to about 1% by weight of active compound.
All plants and plant parts can be treated according to the present invention. Plants are to be understood in the context of the present invention to mean all plants and plant groups such as wild plants or crops (including naturally occurring crops). A crop is a plant obtained by normal plant breeding and optimization methods, by biotechnological and genetic engineering techniques, or by a combination of these methods, including genetically modified plants and plant breeders. Varieties protected by rights or unprotected are included. Plant parts should be understood as meaning all parts and organs of above and below ground plants such as buds, leaves, flowers, roots, leaves, needles, stalks, stems, flowers, fruit bodies, Examples of fruits, seeds, roots, tubers and rhizomes can be given. Plant parts also include harvested materials, vegetative and reproductive propagation materials such as cuttings, tubers, rhizomes, side branches, seeds.
The treatment according to the invention with active compounds of plants and plant parts can be carried out directly or by customary treatment methods such as immersion, spraying, evaporation, spraying, spraying, application, injection, and in the case of propagation materials, in particular seeds. By applying the above coating, it is carried out so that the compound can act on the environment, habitat or storage space.
The active compounds according to the invention are particularly suitable for treating seed. Most of the damage to the crops caused by pests occurs as soon as seeds are attacked during storage, after seeds are sown in the soil, during and immediately after plant germination. This stage is particularly important because the roots and shoots of growing plants are particularly sensitive and even minor damage can lead to the death of the whole plant. It is therefore of great interest to protect seeds and germinating plants with suitable active compounds.

Controlling pests by treating plant seeds has been known for a long time and is the subject of continuous improvement. However, seed treatment involves a series of problems that are not always solved in a satisfactory manner. Therefore, it is desirable to develop a method for protecting seeds and germinating plants that eliminates the need for additional application of crop protection agents after sowing or after plant germination. Furthermore, it is desirable to optimize the amount of active compound used in such a way that the seeds and germinating plants are protected to the maximum from attack by pests without damaging the plant itself by the active compound used. In particular, the method of treating seeds must take into account the inherent insecticidal properties of genetically modified plants in order to achieve optimal protection of seeds and germinating plants using minimal crop protection agents.
The invention therefore also relates to a method of protecting seeds and germinating plants from attack by pests by treating the seeds with the active compounds of the invention. The invention likewise relates to the use of the active compounds according to the invention for the treatment of seeds, which protect the seeds and the resulting plants from pests. Furthermore, the present invention relates to seeds treated with the active compounds of the invention so that they can be protected from pests.
One of the advantages of the present invention is that the specific tissue characteristics of the active compounds of the present invention not only protect the seed itself when treated with these active compounds, but also pests after germination of the resulting plant. It means to protect from. In this way, direct treatment of the crop at or immediately after sowing can be dispensed with.
Furthermore, it must be regarded as advantageous that the active compounds according to the invention can also be used in particular for genetically modified seeds, and that the plants arising from the seeds can express proteins against pests. By treating such seeds with the active compounds according to the invention, certain pests can be simply controlled, for example by the expression of insecticidal proteins, and further protected from damage by the active compounds according to the invention. be able to.

The active compounds according to the invention are suitable for protecting the seeds of any plant species already mentioned which are used in agriculture, greenhouses, forests or horticulture. In particular, this makes corn, peanuts, canola, rapeseed, poppy, soybeans, cotton, beets (e.g. sugar beet, feed beet), rice, sorghum and millet, wheat, barley, oats, rye, sunflower, tobacco, potatoes Alternatively, it takes the form of seeds of vegetables (eg, tomatoes, cabbage plants). Likewise, the active compounds according to the invention are suitable for treating the seeds of the fruit plants and vegetables already mentioned above. The treatment of corn, soy, cotton, wheat and canola or rapeseed seeds is particularly important.
As already mentioned above, the treatment of genetically modified seeds with the active compounds according to the invention is also of particular importance. This typically takes the form of a plant seed containing at least one heterologous gene that governs the expression of a polypeptide having specific insecticidal properties. In this context, heterologous genes in genetically modified seeds are Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus. Alternatively, it may be derived from a microorganism such as Gliocladium. The present invention is suitable for the treatment of genetically modified seeds containing at least one heterologous gene derived from Bacillus species, and whose gene product is active against corn borer and / or root-cut insects.
In the context of the present invention, the active compounds according to the invention are applied to the seed either alone or in a suitable formulation. Preferably, the seed is treated in a state that is sufficiently stable to avoid damage during treatment. In general, seeds can be treated at any point between harvesting and sowing. The seeds used are usually isolated from plants and do not contain cob, shell, handle, skin, hair or fruit pulp.

When treating seeds, in general, the amount of active compound of the invention and / or the amount of other additives applied to the seeds does not adversely affect the germination of the seeds, or the resulting plant is damaged. Care must be taken not to be chosen. This must be particularly noted in the case of active compounds which can have a phytotoxic effect at certain application rates.
As already mentioned above, it is possible to treat all plants and parts thereof according to the invention. In one embodiment, wild plant species and plant varieties, or those obtained by conventional biological breeding methods, such as crossbreeding or protoplast fusion, and portions thereof are treated. In other embodiments, genetic engineering methods treat the resulting genetically modified plants and plant varieties, and portions thereof, where appropriate, in conjunction with conventional methods. In still other embodiments, plants of plant varieties that are commercially available or used in any case are treated according to the present invention. Plant varieties are to be understood as meaning plants having novel characteristics ("traits") obtained by conventional breeding, mutagenesis or recombinant DNA techniques. These can be breeds, biotypes or genotypes.
Depending on the plant species or plant varieties, their location and growth conditions (soil, climate, plant period, nutrients), the treatment of the present invention may provide a synergistic effect. Thus, for example, a reduced application amount, an increased activity spectrum, an increased activity of active compounds and compositions that can be used according to the present invention, better plant growth, increased resistance to high or low temperatures, drought or high soil salt content Increased resistance to, increased flowering performance, easier harvesting, accelerated maturation, higher yield, higher quality and / or higher nutritional value of the harvested product, better storage of the harvested product It is possible to achieve stability and / or processability effects.

  For genetically modified plants or plant varieties (obtained by genetic engineering) that are preferably treated according to the present invention, any genetic material that has been genetically modified to give these plants a particularly advantageous and useful trait has been accepted. Plants are included. Examples of such traits are better plant growth, increased tolerance to high or low temperatures, increased tolerance to drought or high soil salt content, increased flowering performance, accelerated maturation, higher yield, higher Quality and / or higher nutritional value of the harvested product, better storage stability and / or processability of the harvested product. Further and particularly emphasized examples of such traits are the better protection of plants against animals and microbial pests such as insects, ticks, phytopathogenic fungi, bacteria and / or viruses and are active as herbicides. An increase in plant tolerance to the compound. Examples of genetically modified plants are important crops such as cereals (wheat, rice), corn, soybeans, potatoes, sugar beets, tomatoes, peas and other vegetable species, cotton, tobacco, rapeseed, and Fruit plants (fruit apples, pears, citrus and grapes) are mentioned, with particular emphasis on corn, soybeans, potatoes, cotton, tobacco, rape. Traits include toxins formed in plants and genetic material from Bacillus thuringiensis (e.g., genes CryIA (a), CryIA (b), CryIA (c), CryIIA, CryIIIA, CryIIIB2, Cry9c , Cry2Ab, Cry3Bb, CryIF, or combinations thereof) include but are not limited to increased plant protection against insects, arachnids, nematodes, and slugs and snails (hereinafter “ Called "Bt plant"). Traits also include increased plant defense against fungi, bacteria and viruses by systemic acquired resistance (SAR), cystemin, phytoalexin, elicitor and resistance genes and correspondingly expressed proteins and toxins. It is not limited to these. Traits further include, but are not limited to, increased plant tolerance to certain herbicidally active compounds such as imidazolinones, sulfonylureas, glyphosate or phosphinotricin (eg, “PAT” gene). Not. Genes that give the desired trait in question can also be present in combination with each other in transgenic plants. Examples of “Bt plants” include YIEL D GARD® (eg, corn, cotton, soybean), KnockOut® (eg, corn), StarLink® (eg, corn), Bollgard (registered) Mention may be made of corn seed, cotton seed, soybean seed and potato seed sold under the trade names Trademark) (cotton), Nucotn® (cotton) and NewLeaf® (potato). Examples of herbicide-tolerant plants include Roundup Ready® (resistance to glyphosate, e.g. corn, cotton, soybean), Liberty Link® (resistance to phosphinotricin, e.g. rape), IMI® ) (Resistant to imidazolinone) and STS® (resistant to sulfonylureas, eg corn), corn, cotton and soybean. Herbicide-tolerant plants (plants bred in a conventional manner for herbicide tolerance) include species sold under the trade name Clearfield® (eg, corn).

In the field of household insecticides, the active compounds according to the invention can be used alone or with other suitable active compounds, such as phosphate esters, carbamates, pyrethroids, neonicotinoids, growth regulators or other known types of insecticides. Used in combination with the active compound from the agent.
Furthermore, it has also been found that the active compounds according to the invention have a strong insecticidal action against insects that destroy industrial materials.
The following insects: beetles, hymenoptera, termites and stains may be mentioned by way of example but not limitation.
This related industrial material should be understood to mean non-biological materials such as preferably plastics, adhesives, sizing materials, paper and cardboard, leather, wood products, processed wood products, coating compositions. .
The active compounds of the present invention used aerosols, non-pressurized spray products such as pump sprayers, atomizer sprayers, automatic spray devices, sprayers, foams, gels, evaporator tablets made of cellulose or polymers. Evaporator products, liquid evaporators, gel evaporators, membrane evaporators, propeller driven evaporators, energyless or passive evaporators, insect repellent paper, insect repellent bags, repellent gels, dispersed as granules or dust agents Used in bait or at bait station to
Compounds of formula (I), (II), and (III) can be prepared according to known methods (i.e., methods previously used or described in the chemical literature) or described methods, e.g., U.S. Patent No. 6,350,771. One or more applications of the description, 6,750,230, 5,232,940, WO 01/32663 and EP 780 378 (U.S. Pat.No. 5,817,688) or Can be prepared by adaptation. It will be appreciated by those skilled in the art that other methods described in the references cited herein can also be used. Also, the order of the synthetic steps used may vary, in particular the type of other functional groups present in the specific substrate, the availability of key intermediates, and the protecting group strategy to choose (if any). ) factors influenced by the things like will be understood by those skilled in the art (e.g., "Protective Groups in Organic Synthesis ( 3 rd Edition)", Greene and Wuts, ed., Wiley-Interscience, (1999) checking). It is clear that such factors will also affect the choice of reagents used in the synthesis process.

The present invention is further described by the following non-limiting examples illustrating the present invention and should not be construed as limiting the scope of the present invention.
Compounds of formula (I) can be prepared, for example, according to the process described in Scheme 1. Examples of pyrazole derivatives such as (IV) are disclosed in EP 0 295 117 and can be treated with bromine followed by metal thiocyanate. Reduction of thiocyanate can be performed in the presence of a base such as a metal borohydride in an alcohol solvent to produce disulfide (VI). Further, when the disulfide is exposed to a metal borohydride, thiol (VII) can be obtained. Oxidation of thiols to give sulfonyl chlorides can be accomplished using, for example, alkali metal nitrates such as trimethylsilyl chloride and potassium nitrate (see, for example, Journal of Organic Chemistry 2007, 72, 5847 and cited therein). See literature). Alternatively, sulfuryl chloride can be used in place of trimethylsilyl chloride in the oxidation step. The resulting sulfonyl chloride can then be coupled with a linker (IX) containing one terminal amino group (one end protected and shown as “PG”) to give (X). Removal of the protecting group can produce the free amine, which can then be reacted with a second sulfonyl chloride derivative of 1-arylpyrazole to produce the dimer product (I).

Scheme 1. Synthesis of compounds of formula (I).
Compounds of formula (IIa) and (IIb) can be prepared, for example, according to the process described in Scheme 2. For example, a 1-arylpyrazole derivative such as (XI) disclosed in EP 234,119 is treated with vinyltributyltin in the presence of a catalyst such as tetrakis (triphenylphosphine) palladium. Thus, a styryl derivative (XII) is produced. This transformation is recognized in the art as a Still coupling and such a summary can be found in "Metal-Catalyzed Cross Coupling Reactions", F. Diederich and PJ Stang, Wiley-VCH (1998). A Grab's catalyst (see above) can be used to produce a dimer containing a second arylpyrazole such as, for example, (IIa). If necessary, reduction of the olefin may be achieved by hydrogenation to obtain a saturated linker as in (IIb).

Scheme 2. Synthesis of compounds of formula (IIa) and (IIb).
Compounds of formula (III) can be prepared, for example, according to the process described in Scheme 3-5. Halomethylpyrazole derivatives such as (XIII) can serve as a starting point and are disclosed in US Patent Application Publication No. 11 // 825,050 (Scheme 3). A linker (XIV) containing a terminal hydroxyl group (one end protected and shown as “PG”) can be treated with a base such as a metal halide followed by (XIII). The protecting group can be removed to produce the free alcohol (XVI), which is then further reacted with a base such as a metal hydride followed by a second molecule of halomethylpyrazole to produce the dimer. Product (IIIa) can be produced.

Scheme 3. Synthesis of compounds of formula (III) having oxygen-containing linkers.
5-vinylpyrazole derivatives such as (XVII) disclosed in U.S. Patent Application Publication No. 11 // 825,050 serve as substrates for the synthesis of compounds of formula (III) containing a carbon linker. (Scheme 4). Ruthenium-based metathesis reagents such as (XVII) and benzylidene [1,3-bis (2,4,6-trimethylphenyl) -2-imidazolidinylidene] dichloro (tricyclohexylphosphine) ruthenium ("Grubbs Treatment of the dimer product (IIIb), referred to as, for example, Organic Letters 2002, 4, 803; 1999, 1, 953 and 1751; and references cited therein). Can be generated. If necessary, conversion to a saturated derivative can be achieved by reduction with a suitable hydrogen source to obtain the dimer product (IIIc).

Scheme 4. Synthesis of compounds of formula (III) having carbon-containing linkers.
5-Amino-pyrazole derivatives such as (XVIII) are described, for example, in US Pat. Nos. 5,232,940 and 6,346,542, for the synthesis of compounds of formula (III) containing an amine-based linker. Can act as a substrate (Scheme 5). Treatment of (XVIII) with an appropriately protected linker containing a terminal sulfonyl chloride such as (XIX) can produce a sulfonamide such as (XX). After removal of the protecting group, the resulting alcohol can be converted to a halide to give (XXI). The substitution of the halide can be done with thioacetic acid and then converted to the free thiol (XXII). Oxidation to the sulfonyl chloride can be achieved, for example, with an alkali metal nitrate in the presence of trimethylsilyl chloride, followed by treatment with a second 5-aminopyrazole to give the bissulfonamide linked dimer (IIId). it can.

Scheme 5. Synthesis of compounds of formula (III) having a linker containing urea.
The acids, bases, additives, temperatures, and solvents used in the present invention will be apparent to those skilled in the art (e.g., Comprehensive Organic Transformations, RC Larock, VCH Publishers (1989); Vogel's Textbook of Practical Organic Chemistry). (5 ^th Edition), Furniss et al., Longman Scientific & Technical (1989); Protective Groups in Organic Synthesis (3 ^rd Edition), Greene & Wuts, Wiley Interscience (1999); March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6 ^th Edition), March & Smith, Wiley, (2007); Advanced Organic Chemistry (Part A-Structure and Mechanisms-4 ^th Edition), Carey & Sundberg, Springer Science (2000); Advanced Organic Chemistry (Part B- ^{Reaction and Synthesis - 4 th Edition)} , Carey & Sundberg, Springer Science (2001); Strategic Applications of Named Reactions in Organic Synthesis, Kurti and Czako, Academic Press (2005).
The present invention relates to a method of treating animals (eg, mammals or birds) against ectoparasite infections by administering an amount of a composition of the invention effective to combat ectoparasites. Mammals that can be treated include, but are not limited to, humans, cats, dogs, cows, chickens, cows, deer, goats, horses, llamas, pigs, sheep and yaks. In one embodiment of the invention, the mammal to be treated is a human, cat or dog.

In other embodiments of the treatment for ectoparasites, the ectoparasites are Ctenocephalides, Rhipicephalus, Dermacentor, Ixodes, Boophilus, Ambylomma. , Haemaphysalis, Hyalomma, Sarcoptes, Psoroptes, Otodectes, Chorioptes, Hypoderma, Hypoderma, Damalinus, Damalinus One or more insects or arachnids, including the genus Solenoptes, Trichodectes, and Felicola.
In other embodiments of treatment for ectoparasites, the ectoparasite is from Ctenocephalides, Rhipicephalus, Dermacentor, Ixodes and / or Boophilus. It is. The ectoparasites to be treated include, but are not limited to, fleas, ticks, ticks, mosquitoes, flies, lice, black flies and combinations thereof. Individual examples include cat and dog fleas (Ctenocephalides felis, Ctenocephalides sp.), Ticks (Rhipicephalus sp.), Ixodes (Ixodes) sp.), Dermacentor sp., Amblyoma sp., etc.), mites (Demodex, Sarcoptes, Otodictes, etc.), lice (Trichodectes sp.), Kyletiera ( Cheyletiella sp., Lignonathus sp., Etc.), mosquitoes (Aedes sp., Culex sp., Anopheles sp., Etc.) and flies (Hematobia sp. ), Musca sp., Stomoxys sp., Dematobia sp., Cochliomyia sp., Etc.), but are not limited thereto. In yet another embodiment of the treatment for ectoparasites, the ectoparasites are fleas and / or ticks.

Additional examples of ectoparasites include the tick genus Boophilus, especially from the species of microplus (bovine tick), decoloratus and annulatus; Dermatobia hominis (also known as Berne in Brazil) ) And Cochliomyia hominivorax (Cross fly); Miasces such as Lucilia sericata, Lucilia cuprina (also known as Clover Estrecus in Australia, New Zealand and South Africa) But are not limited to these. Natural flies, i.e., adults whose parasites constitute parasites, e.g. lice such as Haematobia irritans (Henmatobia; Linognathus vitul orum); and Sarcoptes scabici, Examples include, but are not limited to, ticks such as Psoroptes ovis The above list is not exhaustive and other ectoparasites harmful to animals and humans are well known in the art These include, for example, the transition dipterous larvae.
When an anthelmintic agent is added to the composition of the present invention, the composition comprises: Anaplocephala, Ancylostoma, Anecator, Ascaris, Capillaria, Cooperia, Dipylidium, Dirofilaria, Echinococcus, Enterobius, Fasciola, Haemonchus, Oesophagostomum, Ostertagia, Toxoa, Toxoka It can also be used to treat endoparasites such as helminths selected from the group consisting of Strongyloides, Toxascaris, Trichinella, Trichuris and Trichostrongylus.

In other embodiments of the present invention, the compounds and compositions of the present invention comprise Blatella germanica, Heliothis virescens, Leptinotarsa decemlineata, Tetramorium caespitum, and Tetramorium caespitum. It is suitable for controlling pests such as insects selected from the group consisting of these combinations.
Plant parasitic nematodes include, for example, Anguina spp., Aphelenchoides spp., Belonoaimus spp., Bursaphelenchus spp., Dityrenx gypsasi ( Ditylenchus dipsaci), Globodera sp., Heliocotylenchus spp., Heterodera spp., Longidorus spp., Meloidogyne spp., Platylenx spp.), Radophorus similis, Rotylenchus spp., Trichodoras sp., Tylenchorhynchus spp., Tylenchulus spp., Tylenchulus spp. Examples include penyltrans (Tylenchulus semipenetrans) and Xiphinema spp.

Furthermore, regardless of the presence or absence of other pesticides added to the composition, the present invention may also be used to treat other pests, including but not limited to the following pests:
(1) From the order of the Isopoda, for example Oniscus asellus, Armadillidium vulgare, Porcellio scaber;
(2) From the order of the Diplopoda, for example Blaniulus guttulatus;
(3) From the order of the Chilopoda, for example, Geophilus carpophagus, Scutigera spp .;
(4) From the order of the Symphyla, for example, Scutigerella immaculata;
(5) Thysanura eyes, such as Lepisma saccharina;
(6) From the order of the Collembola, for example, Onychiurus armatus;
(7) From the order of the Blattaria, for example, Blatta orientalis, Periplaneta americana, Leucopha ea maderae, Blattella germanica;
(8) Hymenoptera, for example, Diprion spp., Hoplocampa spp., Lasius spp., Monomorium pharaonis, Vespa spp .);
(9) From the order of the Siphonaptera, for example, Xenopsylla cheopis, Ceratophyllus spp .;

(10) Anoplura (Phthiraptera), for example, Damarinia spp., Haematopinus spp., Linognathus spp., Pediculus spp. Species (Trichodectes spp.);
(11) Of the Arachnida class, e.g. Acarus siro, Aceria sheldoni, Aculops spp., Aculus spp., Amblyomma spp ), Argas spp., Boophilus spp., Brevipalpus spp., Bryobia praetiosa, Chorioptes spp., Dermanyssus gallinae , Eotetranychus spp., Epitrimerus pyri, Eutetranychus spp., Eriophyes spp., Hemitarsonemus spp., Hyalomma sp .), Ixodes spp., Latrodectus mactans, Metatetranychus spp., Oligonychus spp., Ornitho Rossi (Ornithodoros spp.), Panonychus (Panonychus spp.), Phyllocoptruta oleivora, Polyphagotarsonemus latus, Psoroptes spp. , Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Stenotarsonemus spp., Tarsononemus spp., Tetranics sp. ), Vasates lycopersici;
(12) From the Vivalba class, e.g. Dreissena spp .;

(13) From the order of the Coleoptera, for example, Acanthoscelides obtectus, Adoretus spp., Agelastica alni, Agriotes spp., Amphimaron sp. Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp., Anthrenus spp., Apogonia sp. (Atomaria spp.), Atagenus (Attagenus spp.), Bruchidius obtectus (Bruchus spp.), Seutrinkus (Ceuthorhynchus spp.), Cleonus mendicus (Cleonus mendicus), Conodels Conoderus spp.), Cosmopolites spp., Costelytra zealandica, Curculio spp. rculio spp.), Cryptorhynchus lapathi, Dermestes spp., Diabrotica spp., Epilachna spp., Faustinus cubae Gibbium psylloides), Heteronychus arator, Hylamorpha elegans, Hylotrupes bajulus, Hipera postica, Hypotenum sans ), Leptinotarsa decemlineata, Lissorhoptrus oryzophilus, Lixus spp., Lyctus spp., Melitethes aeneus Migdolus spp ), Monochamus spp., Naupactus xanthographus, Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surmenus, Oryzaephilus surina (Otiorrhynchus sulcatus), Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Popilia japonica, Premnotry pes p chrysocephala, Petinus spp., Rhizobius ventralis, Rhizopertha dominica, Sitophilus spp., Sphenophorus spp., Sternech sp .), Shin fillet (Symphyletes spp.), Tenebrio molitor (Tribolium spp.), Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus ( Zabrus spp.);

(14) From the order of the Diptera, for example, Aedes spp, Anopheles spp., Bibio hortulanus, Calliphora erythrocephala, Serachitis capita Ceratitis capitata), Chrysomyia spp., (Cochliomyia spp.), Cordylobia anthropophaga, Culex spp., Cuterebra spp., Dacus oleae, Dermatobia hominis, Drosophila spp., Fannia spp., Gastrophilus spp., Hylemyia spp., Hypobosca spp., Hipobosca spp. Species (Hypoderma spp.), Liriomyza spp., Lucilia spp., Musca spp., Nezara spp., Oestrus spp., Oscine Oscinella frit, Pegomyia hyoscyami, Phorbia spp., Stomoxys spp., Tabanus spp., Tannia spp., Chipra Pardosa (Tipula paludosa), Wohlfahrtia spp .;
(15) Of Gastropoda class, e.g. Arion spp., Biomphalaria spp., Bulinus spp., Deroceras spp., Galba spp .), Limnaea spp., Oncomelania spp., Succinea spp .;

(16) From the class of helminths, e.g., Ancylostoma duodenale, Ancylostoma ceylanicum, Acylostoma braziliensis, Alostoma sp. Lubrichoides (Ascaris lubricoides), Ascaris spp., Brugia malayi, Brugia timori, Bunostomum spp., Chabertia spp., Clonorchis spp.), Cooperia spp., Dicrocoelium spp, Dictyocaulus filaria, Diphyllobothrium latum, Dracunculus medinensis, Dracunculus medinensis (Echinococcus granulosus), Echinococcus Echinococcus multilocularis, Enterobius vermicularis, Faciola spp., Hemonakis spp., Heterakis spp., Hymenolepis nana, Hymenolepis nana, Hymenolepis nana Hyostrongulus spp., Loa Loa, Nematodirus spp., Oesophagostomum spp., Opisthorchis spp., Onchocerca volvulus , Ostertagia spp., Paragonimus spp., Schistosomen spp., Strongyloides fuelleborni, Strongyloides stercoralis, Strongyloides stercoralis Stronyloides spp.), Taenia saginata, Taenia solium), Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella nelsone, Trichinella pseudopsiralis (Trichinella pseudopsiralis), Tricostella spp. Trichostrongulus spp.), Wuchereria bancrofti, Wuchereria bancrofti;

(17) From the order of the Heteropter, for example, Anasa tristis, Antestiopsis spp., Blissus spp., Calocoris spp., Campyromma libida (Campylomma livida), Cavelerius spp., Cimex spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Dychelops furcatus (Diconocoris hewetti), Dysdercus spp., Euschistus spp., Eurygaster spp., Heliopeltis spp. spp.), Leptoglossus phyllopus, Lygus spp., Macropes excavatus , Milidae, Nezara spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., Perias stus , Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scotinophora spp., Stephanitis nashi, Tibraca sp. ), Triatoma spp.);

(18) From the order of the Homoptera class, for example, Acyrthosipon spp., Aeneolamia spp., Agonoscena spp., Aleurodes spp., Aleurobus barolodensis barodensis), Aleurothrixus spp., Amrasca spp., Anuraphis cardui, Aonidiella spp., Aphanostigma piri, Aphis species A spp.), Arboridia apicalis, Aspidiella spp., Aspidiotus spp., Atanus spp., Aulacorthum solani, Bemisia sp. ), Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae Calligypona marginata, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Cercopidae, Cheroplastis phon, fragrant tegalensis), Chlorita onukii, Chromaphis juglandicola, Chrysomphalus ficus, Cicadulina mbila, Coccomytilus halloween (Coccomytilus halloween) Coccus spp., Cryptomyzus ribis, Dalbulus spp., Dialeurodes spp., Diaphorina spp., Diaspis spp., Drosicha spp. ), Dysaphis spp. Species (Dysmicoccus spp.), Empoasca spp., Eriosoma spp., Erythroneura spp., Eucelis bilobatus, Geococcus coffae officio Coagulata (Homalodisca coagulata), Hyalopterus arundinis, Icerya spp., Idiocerus spp., Idioscopus spp., Laodelfax striatels (Laodel) Species (Lecanium spp.), Lepidosaphes spp., Lipaphis erysimi, Macrosiphum spp., Mahanarva fimbriolata,

Melanaphis sacchari, Metcalfiella spp., Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Monelliopsis pecanis, Monelliopsis pecanis, Nasonovia ribisnigri, Nephotettix spp., Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Parabemicia miriae, ab spp.), Parlatria spp., Pemphigus spp., Peregrinus maidis, Phenacoccus spp., Phlooeomyzus passerinii, Forodon P humuli), a phylloxera species (Phylloxera spp.), Pinnaspis aspidistrae, Planococcus spp., Protopulvinaria pyriformis, Pseudaulacaspis pentagonoccus, Pseudaulacaspis pentagonoccus spp.), Shira species (Psylla spp.), Pteromalus spp., Pyrilla spp., Quadraspidiotus spp., Quesada gigas, Rastrococcus species (Rastrococcus spp.), Rhopalosiphum spp., Saissetia spp., Scaphoides titanus, Schizaphis graminum, Selizaspis articus (Selenaspus articus spp.),
Sogaterella furcifera, Sogatodes spp., Stictocephala festina, Tenalaphara malayensis, Tinocallis carpia sp. , Toxoptera spp., Trieureurodes vaporarjorum, Trioza spp., Typhlocyba spp., Unaspis spp.

(19) From the order of the Isoptera, for example, Reticulitermes spp., Odontotermes spp.
(20) From the order of the Lepidoptera, for example, Acronis ta major, Aedia leucomelas, Agrotis spp., Alabama argillacea, Anticarsia spp.), Barathra brassicae, Bucculatrix thurberiella, Bupalus piniarius, Cacoecia podana, Capua reticulana, Carpocapsa pomonella, Cheimatobia brumata, Chilo spp., Choristoneura fumiferana, Clysia ambiguella, Cnasia ambiguella, Cnaphalocerus spp. ), Ephesti Queniera a kuehniella, Euproctis chrysorrhoea, Odontotermes spp., Feltia spp., Galleria mellonella, Helicoverpa spp., Heliocovera spp. spp.), Hofmannophila pseudospretella, Homona magnanima, Hyponomeuta padella, Laphygma spp., Lithocolletis blanca・ Lithophane antennata, Loxagrotis albicosta, Lymantria spp., Malacosoma neustria, Mamestra brassicae, Mocis repanda, Micis repanda Mythimna separata, Oria spp. Oulema oryzae, Panolis flammea, Pectinophora gossypiella, Phyllocnistis citrella, Pieris spp., Ella Plutella, plutera (Prodenia spp.), Pseudaletia spp., Pseudoplusia includens, Pyrausta nubilalis, Spodoptera spp., Thermesia gemmatalis, Thermesia gemmatalis Tinea pellionella, Tineola bisselliella, Tortrix viridana, Trichoplusia spp .;

(21) From the order of the Orthoptera, for example, Acheta domesticus, Bratta orientalis, Blattella germanica, Gryllotalpa spp., Leucophaea Maderae maderae), Locusta spp., Melanoplus spp., Periplaneta americana, Schistocerca gregaria.
(22) Thysanoptera, e.g., Variothrips biformis, Enneothrips flavens, Frankliniella spp., Helioslips spp., Helisrips spp.・ Femolaris (Hercinothrips femoralis), cacoslip species (Kakothrips spp.), Lipiphoroslips cruentatus, Siltothrips species (Scirtothrips spp.);
(23) From the Protozoa class, for example, Eimeria spp.

Where appropriate, the compounds of the invention may be herbicides, safeners, growth regulators or agents that improve plant properties, or fungicides such as fungicides, antifungals, at certain concentrations or dosages. It can also be used as a bactericidal agent, a virucidal agent (including drugs against viroids) or as a drug against MLO (mycoplasma-like microorganisms) and RLO (rickettsia-like microorganisms). Where appropriate, they can also be used as intermediates or precursors for the synthesis of other active compounds.
In each aspect of the invention, the compounds and compositions of the invention can be applied to a single pest or a combination thereof.
The active compounds of the present invention combine good plant resistance and good tolerance to warm-blooded animals and well tolerated environment to protect plants and plant organs, increase yields, and quality of harvested materials Animal pests, especially insects, arachnids, helminths, nematodes and mollusks encountered in the agriculture, horticulture, livestock, forest, orchard and leisure facilities, protection of stored products and materials, hygiene sector Suitable for extinguishing. Preferably, it can be used as a plant protection agent. They are active against normally sensitive and resistant species and against all or certain stages of development.
The invention is further described by the following numbered sections:
(1) a compound of formula (I); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n - and -S ( O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(2) The compound of item (1); or a salt thereof:
R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently selected from the group consisting of halogen, cyano, nitro, R ₇ , R ₈ , —C (O) R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl and heteroaryl groups may optionally be independently substituted with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a are _{independently, -C (= NR 7) -} , - C (= NR 8) -, - C (= O) -, - C (= O) NR 11 -, - C ( _{= S) NR 11 -, -} S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(3) The compound of item (1); or a salt thereof:
R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are independently selected from the group consisting of halogen, haloalkyl, —S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently selected from the group consisting of alkyl, haloalkyl, —NR ₁₁ R ₁₂ , and —N═C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl groups are independently one or more selected from the group consisting of R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted by
R ₇ is selected from the group consisting of H and alkyl;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) nNR ₁₁ R ₁₂ , -C ( = O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Is;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are _{independently, -C (= NR 7) -} , - C (= NR 8) -, - C (= O) -, - C (= O) NR 11 -, - C ( _{= S) NR 11 -, -} S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, May contain S, P or Si atoms;
Here, the linker is optionally substituted independently with one or more groups selected from hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. May be;
n is independently 0, 1 or 2.

(4) The compound of item (1); or a salt thereof:
R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are hydrogen;
R ₁₃ and R _13a are -S (O) _n- ;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
The linker is optionally independently one or more groups selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. May be substituted;
n is independently 0, 1 or 2.
(5) The compound of item (1); or a salt thereof:
R ₁ and R _1a are cyano;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are hydrogen;
R ₁₃ and R _13a are -S (O) _n- ;
L is alkyl or haloalkyl;
n is 2.
(6) a compound of formula (II); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(7) The compound of item (6); or a salt thereof:
R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R7, -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , and -N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a bond, -O -, - S (O ) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, May contain S, P or Si atoms;
The linker is optionally independently one or more groups selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. May be substituted;
n is independently 0, 1 or 2.

(8) The compound of item (6); or a salt thereof:
R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, haloalkyl, —NR ₁₁ R ₁₂ , and —N═C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
The alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group and heteroaryl group are independently selected from the group consisting of R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted by one or more groups;
R ₇ is selected from the group consisting of H and alkyl;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may optionally be independently substituted with one or more groups from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a is independently a bond, -O -, - S (O ) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(9) The compound of item (6); or a salt thereof:
R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl and haloalkyl;
R ₁₃ and R _13a are independently selected from the group consisting of a bond and -S (O) _n- ;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, Can contain S atoms, P atoms or Si atoms;
Here, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino and alkoxyimino, if necessary. Optionally substituted with a group;
n is independently 0, 1 or 2.

(10) The compound of item (6); or a salt thereof:
R ₁ and R _1a are cyano;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are a bond;
L is alkyl or haloalkyl;
n is 2.
(11) a compound of formula (III); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl and heteroaryl groups may optionally be independently substituted with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) nNR ₁₁ R ₁₂ , -C ( _{= O) R 11, -C (} = O) OR 11, -C (= O) NR 11 R 12, -C (= S) R 11, selected from the group consisting of _{-C (= S) NR 11 R} 12 Is;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 SO} 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) - , -C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - C (= NR 7) NR 11 -, - S (O) n -, and - S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(12) The compound of item (11); or a salt thereof:
R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ and -C (S) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently selected from the group consisting of halogen, R ₇ , R ₈ , —S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group are independently selected from R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 SO} 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) - , -C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - C (= NR 7) NR 11, -S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally includes one or more N atoms, O atoms, May contain S, P or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(13) The compound of item (11); or a salt thereof:
R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-diacyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are independently selected from the group consisting of halogen, haloalkyl, —S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and alkyl;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a is independently a _{bond, -NR 11 SO 2 NR 11 -} , - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) -, - C ( _{= O) NR 11 -, -} C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.

(14) The compound of item (11); or a salt thereof:
R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are a bond;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2.
(15) a compound of formula (11); or a salt thereof:
R ₁ and R _1a are cyano;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
Z and Z ₁ are CR ₃ ;
R ₁₁ is haloalkyl;
R ₁₃ and R _13a are a bond;
L is alkyl or haloalkyl;
n is 2.

(16) A composition for treating an animal against ectoparasites comprising the compound according to any one of Items 1-15 and an acceptable carrier.
(17) The composition according to item 16, wherein the composition is a topical preparation, a transdermal preparation or a subcutaneous preparation.
(18) The composition according to item 16, wherein the composition is a microemulsion, paste, pour-on formulation, ready-to-use formulation, spot-on formulation, oral solution, emulsion, solution for injection, suspension or enteric formulation.
(19) The composition according to item 16, further comprising an additional insecticidal active ingredient.
(20) The composition according to item 19, wherein the insecticidal active ingredient is arylpyrazole, nozurisporic acid or a derivative thereof, macrocyclic lactone, formamidine, pyrethroid, insect growth regulator, benzenedisulfonamide compound, tapeworm repellent, Item 20. The composition according to Item 19, selected from the group consisting of a pyridylmethyl derivative, a depsipeptide, and a mixture thereof.
(21) Use of the composition according to any one of Items 16-20 in the manufacture of a medicament for therapeutically and / or prophylactically treating an animal against ectoparasites and / or endoparasites.
(22) The use according to item 21, wherein the treatment is for an ectoparasite selected from the group consisting of arthropods, mites and mixtures thereof.
(23) The use according to item 21, wherein the ectoparasite is selected from the group consisting of fleas, flies, lice, ticks and ticks.
(24) The use of paragraph 21, wherein the treatment is for endoparasites.
(25) An insecticide composition comprising the compound according to any one of Items 1-15 and an acceptable carrier.
(26) Use of any one of the compounds according to Item 1-15 in the manufacture of a composition for controlling pests.
(27) A method for preparing an insecticidal composition, wherein the compound according to any one of Items 1-15 is mixed with a bulking agent and / or a surfactant.
(28) A method for controlling pests, wherein the compound according to any one of Items 1 to 15 or the composition of Item 25 is applied to the pests and / or the environment thereof, or plants, plant parts, seeds, soil, regions, and materials. Or the said method of making it act on space and keeping it in the state without a pest.
(29) Use of any one of the compounds according to Item 1-15 or the composition defined in Item 25 for controlling pests.
(30) A method for the treatment or prevention of parasite propagation or infection in an animal, comprising administering an effective amount of any one of the compounds of paragraphs 1-15 to an animal in need thereof .
***
Thus, while various embodiments of the invention have been described in detail, the invention, as defined by the above paragraphs, is intended to allow many obvious modifications without departing from the spirit or scope of the invention. It should be understood that the invention is not limited to the specific details set forth in the foregoing description.

Claims (30)

A compound of formula (I); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₇ ) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2. R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently selected from the group consisting of halogen, R ₇ , R ₈ , —C (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( _{= NR 7) NR 11 R 12} , -C (= S) NR 11 R 12, selected from the group consisting of -NR ₁₁ R ₁₂ and _{-N = C (R 11) NR} 6,;
Z and Z ₁ are CR ₃ ;
R ₁₃ and R _13a are _{independently, -C (= NR 7) -} , - C (= NR 8) -, - C (= O) -, - C (= O) NR 11 -, - C ( _{= S) NR 11 -, -} S (O) n -, and -S (O) _n NR ₁₁ - compound of claim 1 selected from the group consisting of; or a salt thereof. R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are independently selected from the group consisting of halogen, haloalkyl, —S (O) _n R ₁₁ , and SF ₅ ;
R ₅ and R _5a are independently selected from the group consisting of alkyl, haloalkyl, —NR ₁₁ R ₁₂ , and —N═C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are _{independently, -C (= NR 7) -} , - C (= NR 8) -, - C (= O) -, - C (= O) NR 11 -, - C ( _{= S) NR 11 -, -} S (O) n -, and -S (O) _n NR ₁₁ - compound of claim 1 selected from the group consisting of; or a salt thereof. R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are hydrogen;
2. The compound according to claim 1, wherein R ₁₃ and R _13a are —S (O) _n —; or a salt thereof. R ₁ and R _1a are cyano;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are hydrogen;
R ₁₃ and R _13a are -S (O) _n- ;
L is alkyl or haloalkyl;
2. The compound according to claim 1, wherein n is 2, or a salt thereof. A compound of formula (II); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( = NR ₇ ) NR ₁₁ R ₁₂ , -C (= S) NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ C (= O) R ₈ , -NR ₁₁ C (= O) R ₁₁ , and- Selected from the group consisting of N = C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 -} , - NR 11 C (= O) -, - NR 11 C (= S) -, - NR 11 C (= O) _{O -, - NR 11 C (} = O) NR 11 -, - NR 11 C (= S) NR 11 -, - NR 11 SO 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) _{-, - C (= NR 8} ) -, - C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms, or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2. R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₅ and R _5a are independently R ₁₀ , R ₁₁ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , -C ( _{= NR 7) NR 11 R 12} , -C (= S) NR 11 R 12, selected from the group consisting of -NR ₁₁ R ₁₂ and _{-N = C (R 11) NR} 6,;
Z and Z ₁ are CR ₃ ;
R ₁₃ and R _13a are independently chosen from a bond, -O -, - S (O ) n -, and -S (O) _n NR ₁₁ - compound of claim 6 selected from the group consisting of; or Its salt. R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, haloalkyl, —NR ₁₁ R ₁₂ , and —N═C (R ₁₁ ) NR ₆ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are independently chosen from a bond, -O -, - S (O ) n -, and -S (O) _n NR ₁₁ - compound of claim 6 selected from the group consisting of; or Its salt. R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
7. The compound according to claim 6, wherein R ₁₃ and R _13a are independently selected from the group consisting of a bond and —S (O) _n —; or a salt thereof. R ₁ and R _1a are cyano;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are halogen;
R ₅ and R _5a are independently selected from the group consisting of alkyl, and -NR ₁₁ R ₁₂ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are a bond;
L is alkyl or haloalkyl;
7. The compound according to claim 6, wherein n is 2, or a salt thereof. A compound of formula (III); or a salt thereof:

Wherein R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , —C (═O) R ₆ , —C (═O) R ₈ , —C (═O) NR ₁₁ R ₁₂ , -CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ ,- Selected from the group consisting of C (= NNR ₇ ) R ₇ , -C (= NNR ₇ ) R ₈ , -C (= NNR ₈ ) R ₇ , and -C (S) NR ₇ R ₁₁ ;
R ₂ and R _2a are independently selected from the group consisting of S (O) _n R ₁₁ , and 4,5-dicyanoimidazol-2-yl;
R ₃ and R _3a are independently selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, haloalkyl, alkoxy, and haloalkoxy;
R ₄ and R _4a are independently halogen, cyano, nitro, R ₇ , R ₈ , -C (O) R ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR7) NR ₁₁ R ₁₂ , -S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are independently selected from the group consisting of a nitrogen atom and CR ₃ ;
R ₆ is selected from the group consisting of alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, alkynyl, aryl and heteroaryl;
Here, the alkyl group, haloalkyl group, cycloalkyl group, halocycloalkyl group, alkenyl group, alkynyl group, aryl group, and heteroaryl group independently comprise R ₈ , R ₉ and R ₁₀ as necessary. Optionally substituted with one or more groups selected from the group;
R ₇ is selected from the group consisting of H and R ₆ ;
R ₈ is selected from the group consisting of -OR ₉ , -OR ₁₁ , -SR ₉ , -SR ₁₁ , -NR ₉ R ₁₁ , and -NR ₁₁ R ₁₂ ;
R ₉ is selected from the group consisting of aryl and heteroaryl;
Here, the aryl group and heteroaryl group may be optionally substituted independently with one or more groups selected from the group consisting of R ₁₀ and R ₁₁ ;
R ₁₀ is cyano, nitro, hydroxyl, halogen, alkyl, cycloalkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) _n R ₁₁ , -S (O) _n NR ₁₁ R ₁₂ , -NR ₁₁ R ₁₂ , -NR ₁₁ (C = O) R ₁₁ , -NR ₁₁ (C = O) NR ₁₁ R ₁₂ , -NR ₁₁ S (O) _n R ₁₁ , -NR ₁₁ S (O) _n NR ₁₁ R ₁₂ , -C (= O) R ₁₁ , -C (= O) OR ₁₁ , -C (= O) NR ₁₁ R ₁₂ , -C (= S) R ₁₁ , -C (= S) NR ₁₁ R ₁₂ Chosen;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkenyl, haloalkenyl, alkynyl, and haloalkynyl;
R ₁₃ and R _13a is independently a _{bond, -O -, - NR 11 SO} 2 NR 11 -, - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) - , -C (= O) -, - C (= O) NR 11 -, - C (= S) NR 11 -, - C (= NR 7) NR 11, -S (O) n -, and -S (O) _n NR ₁₁ - selected from the group consisting of;
L is a linker selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aryloxyaryl, heteroaryl, and combinations thereof, which optionally contain one or more N atoms, O atoms , May contain S atoms, P atoms or Si atoms;
Here, if necessary, the linker is independently one or more selected from cyano, nitro, hydroxy, halogen, O, N, S, alkyl, cycloalkyl, alkoxy, thioalkyl, oxo, oxyimino, and alkoxyimino. Optionally substituted by
n is independently 0, 1 or 2. R ₁ and R _1a are independently hydrogen, cyano, halogen, R ₆ , -C (= O) R ₆ , -C (= O) R ₈ , -C (= O) NR ₁₁ R ₁₂ ,- CH (= NR ₇ ), -CH (= NR ₈ ), -C (= NR ₇ ) R ₇ , -C (= NR ₇ ) R ₈ , -C (= NR ₈ ) R ₇ , and -C (S ) Selected from the group consisting of NR ₇ R ₁₁ ;
R ₄ and R _4a are independently selected from the group consisting of halogen, R ₇ , R ₈ , —S (O) _n R ₁₁ , and SF ₅ ;
12. The compound according to claim 11, wherein Z and Z ₁ are CR ₃ ; or a salt thereof. R ₁ and R _1a are independently selected from the group consisting of cyano, halogen, and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are independently selected from the group consisting of halogen, haloalkyl, —S (O) _n R ₁₁ , and SF ₅ ;
Z and Z ₁ are CR ₃ ;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
R ₁₃ and R _13a are independently chosen from a _{bond, -NR 11 SO 2 NR 11 -} , - NR 11 SO 2 -, - C (= NR 7) -, - C (= NR 8) -, - C ( _{= O) NR 11-, -C (} = S) NR 11 -, - S (O) n -, and -S (O) _n NR ₁₁ - compound according to claim 11, chosen from the group consisting of; or salt. R ₁ and R _1a are independently selected from the group consisting of cyano and -C (S) NR ₇ R ₁₁ ;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
Z and Z ₁ are CR ₃ ;
R ₇ is selected from the group consisting of H and alkyl;
R ₁₁ and R ₁₂ are independently selected from the group consisting of hydrogen, alkyl, and haloalkyl;
12. The compound according to claim 11, wherein R ₁₃ and R ₁₃ are a bond; or a salt thereof. R ₁ and R _1a are cyano;
R ₃ and R _3a are halogen;
R ₄ and R _4a are haloalkyl;
Z and Z ₁ are CR ₃ ;
R ₁₁ is haloalkyl;
R ₁₃ and R _13a are a bond;
L is alkyl or haloalkyl;
12. The compound according to claim 11, wherein n is 2, or a salt thereof.   A composition for treating or preventing parasite growth or infection in an animal comprising the compound of any one of claims 1-15 and an acceptable carrier.   17. The composition according to claim 16, wherein the composition is a topical preparation, a transdermal preparation, or a subcutaneous preparation.   17. The composition of claim 16, wherein the composition is a microemulsion, paste, pour-on formulation, ready-to-use formulation, spot-on formulation, oral solution, emulsion, injectable solution, suspension or enteric formulation.   17. The composition of claim 16, further comprising an additional insecticidal active ingredient.   Additional insecticidal active ingredients include arylpyrazoles, nozurisporic acid or derivatives thereof, macrocyclic lactones, formamidines, pyrethroids, insect growth regulators, benzenedisulfonamide compounds, stripworms, pyridylmethyl derivatives, depsipeptides and these 20. A composition according to claim 19, selected from the group consisting of a mixture.   21. Use of a composition according to any one of claims 16-20 in the manufacture of a medicament for treating an animal against parasite reproduction or infection.   The use according to claim 21, wherein the treatment is against an ectoparasite selected from the group consisting of arthropods, mites and mixtures thereof.   The use according to claim 21, wherein the ectoparasite is selected from the group consisting of fleas, flies, lice, ticks and ticks.   The use according to claim 21, wherein the treatment is against endoparasites.   An insecticide composition comprising the compound of any one of claims 1-15 and an acceptable carrier.   Use of a compound according to any one of claims 1-15 in the manufacture of a composition for combating pests.   A method for preparing an insecticidal composition, wherein the compound according to any one of claims 1-15 is mixed with a bulking agent and / or a surfactant.   A method for combating pests, wherein the compound according to any one of claims 1-15 or the composition according to claim 25 is applied to pests and / or their environment or to plants, plant parts, seeds, soil. The method, wherein the method is applied to a region, material, or space to keep the pest free.   Use of a compound according to any one of claims 1-15 or a composition according to claim 25 for combating pests.   A method for the treatment or prevention of parasite propagation or infection in an animal comprising administering an effective amount of a compound according to any one of claims 1-15 to an animal in need thereof. Method.